WO2023183396A1

WO2023183396A1 - Compositions and methods of treating inflammation using prevotella histicola

Info

Publication number: WO2023183396A1
Application number: PCT/US2023/015918
Authority: WO
Inventors: S.M. Abel; Douglas MASLIN; Duncan MCHALE; Yanislav Mihaylov; Jonathan ZUNG
Original assignee: Evelo Biosciences, Inc.
Priority date: 2022-03-22
Filing date: 2023-03-22
Publication date: 2023-09-28

Abstract

Provided herein are methods and compositions related to Prevotella bacteria useful as therapeutic agents, e.g., for the treatment of inflammatory disease.

Description

COMPOSITIONS AND METHODS OF TREATING INFLAMMATION USING

PREVOTELLA HISTICOLA

CROSS-REFERENCE TO RELATED APPLICATIONS

[1] This application claims the benefit of U.S. Provisional Application No. 63/322,465, filed on March 22, 2022, the content of which is hereby incorporated by reference in its entirety.

SUMMARY

[2] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of an inflammatory disease. In some embodiments, the inflammatory disease is a Thl, Th2, or Th 17 inflammatory disease. As described herein, the bacterial compositions can be used for at least 20 weeks.

[3] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of an immune disorder. As described herein, the bacterial compositions can be used for at least 20 weeks.

[4] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g, for the treatment of psoriasis, for the reduction of Lesion Severity Scores (LSS), and/or for the reduction of Psoriasis Area Severity Index (PASI) scores). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[5] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis) (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of atopic dermatitis and/or for an improvement in EASI score). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[6] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of psoriatic arthritis (e.g., mild to moderate psoriatic arthritis, or mild, moderate, or severe psoriatic arthritis) (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of psoriatic arthritis). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[7] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of an autoimmune disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of an autoimmune disease). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[8] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of an inflammatory disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of an inflammatory disease). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[9] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of a metabolic disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a metabolic disease). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, attenuated and/or bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks. [10] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of a dysbiosis, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a dysbiosis). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[11] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels), (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels)). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[12] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for decreasing IgE levels (e.g., mRNA or protein levels) (e.g., in a subject, e.g., a human subject), and methods of using such bacterial compositions (e.g., for decreasing IgE levels (e.g., mRNA or protein levels)). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[13] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of bacterial septic shock, cytokine storm and/or viral infection). In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[14] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola useful for the treatment and/or prevention of a viral infection, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a viral infection). In some embodiments, the viral infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection. In some embodiments, the viral infection is a SARS-CoV-2 infection. In some embodiments, the bacterial compositions comprise whole Pre votella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). As described herein, the bacterial compositions can be used for at least 20 weeks.

[15] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 20 weeks. In some embodiments, the bacterial composition e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 24 weeks. In some embodiments, the bacterial composition e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 28 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 32 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 36 weeks. In some embodiments, bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 40 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 44 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 48 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 52 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for at least 56 weeks. For example, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject once daily for the given number of weeks. For example, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject twice daily for the given number of weeks.

[16] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 20 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 24 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 28 weeks. In some embodiments, the bacterial composition e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 32 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 36 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 40 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 44 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 48 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 52 weeks. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject for 56 weeks. For example, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject once daily for the given number of weeks. For example, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola is administered to the subject twice daily for the given number of weeks.

[17] In some embodiments, the Prevotella histicola is Prevotella Strain B 50329 (NR.R.L accession number B 50329; Strain B). In some embodiments, the Prevotella strain is a strain comprising at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella Strain B 50329.

[18] In some embodiments, the bacterial composition comprises one strain of bacteria, wherein the one strain of bacteria is a strain comprising at least 99.9% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NR.R.L accession number B 50329). In some embodiments, the bacterial composition comprises one strain of bacteria, wherein the one strain of bacteria is the Prevotella histicola Strain B 50329 (NRRL accession number B 50329).

[19] In some embodiments, the bacterial compositions are prepared as solid dosage forms. In some embodiments, provided herein are solid dosage forms comprising the Prevotella histicola bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, each tablet comprises about 3.2 x 10¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, the solid dosage form is a capsule e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x IO¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 3.2 x 10¹¹ total cells (e.g., 3.35 x 10¹¹ total cells) of the Prevotella histicola bacteria.

[20] In some embodiments, from 1.6 x IO¹⁰ cells to 16 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 8 x 10¹¹ cells to 16 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 8 x IO¹⁰ cells to 8 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 3.2 x IO¹⁰ cells to 9.6 x IO¹⁰ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 4.8 x IO¹⁰ cells to 9.6 x IO¹⁰ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 6.4 x IO¹⁰ cells to 9.6 x IO¹⁰ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 8 x IO¹⁰ cells to 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, from 1.6 x 10¹¹ cells to 8 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 8 x IO¹⁰ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 3.2 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 6.4 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form. In some embodiments, about 8 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject daily, e.g., in a solid dosage form.

[21] In some embodiments, about 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject once daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily, e.g., in a solid dosage form. In some embodiments, about 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject twice daily (e.g., for 1- 7 days, 3 days, 7 days, 10 days, or 14 days), and then about 1.6 x 10¹¹ cells of the Prevotella histicola strain are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment), e.g., in a solid dosage form.

[22] In some embodiments, about 8 x IO¹⁰ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[23] In some embodiments, about 1.6 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[24] In some embodiments, about 3.2 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[25] In some embodiments, about 6.4 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[26] In some embodiments, about 9.6 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[27] In some embodiments, about 12.8 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[28] In some embodiments, about 16 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[29] In some embodiments, about 3.2 x IO¹⁰ to about 9.6 x IO¹⁰ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[30] In some embodiments, about 4.8 x IO¹⁰ to about 9.6 x IO¹⁰ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily. [31] In some embodiments, about 6.4 x IO¹⁰ to about 9.6 x IO¹⁰ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[32] In some embodiments, about 1.6 x 10¹¹ to about 6.4 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[33] In some embodiments, about 8 x IO¹⁰ to about 8 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[34] In some embodiments, about 9.6 x 10¹¹ to about 16 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[35] In some embodiments, about 9.6 x 10¹¹ to about 12.8 x 10¹¹ total cells of the Prevotella histicola strain are administered to the subject daily.

[36] In some embodiments, about 12.8 x 10¹¹ to about 16 x 10¹¹ total cells of the Prevotella histicola strain (e.g., in a solid dosage form) are administered to the subject daily.

[37] In some embodiments, the bacterial composition comprises about 1.6 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[38] In some embodiments, the bacterial composition comprises about 8 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[39] In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[40] In some embodiments, the bacterial composition comprises about 3.2 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[41] In some embodiments, the bacterial composition comprises about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[42] In some embodiments, the bacterial composition comprises about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form). [43] In some embodiments, the bacterial composition comprises about 3.2 x IO¹⁰ to about

9.6 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[44] In some embodiments, the bacterial composition comprises about 4.8 x IO¹⁰ to about

[45] In some embodiments, the bacterial composition comprises about 6.4 x IO¹⁰ to about

[46] In some embodiments, the bacterial composition comprises about 1.6 x IO¹⁰ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[47] In some embodiments, the bacterial composition comprises about 1.6 x IO¹⁰ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[48] In some embodiments, the bacterial composition comprises about 1.6 x 10¹⁰ to about

1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[49] In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[50] In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ to about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[51] In some embodiments, the bacterial composition comprises about 8 x 10¹⁰ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329 (e.g., in a solid dosage form).

[52] In some embodiments, the bacterial composition is provided as a solid dosage form (also referred to as a solid dose form). In some embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form comprises an enteric coating (e.g., HPMC coat). [53] In some embodiments, the solid dosage form comprises between about 3.2 x IO¹⁰ and about 9.6 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[54] In some embodiments, the solid dosage form comprises between about 4.8 x IO¹⁰ and about 9.6 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[55] In some embodiments, the solid dosage form comprises between about 6.4 x IO¹⁰ and about 9.6 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[56] In some embodiments, the solid dosage form comprises between about 8 x IO¹⁰ and about 3.2 x 10ⁿtotal cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[57] In some embodiments, the solid dosage form comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[58] In some embodiments, the solid dosage form comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[59] In some embodiments, the solid dosage form comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[60] In some embodiments, the solid dosage form comprises about 6.4 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[61] In some embodiments, the solid dosage form comprises about 8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[62] In some embodiments, the solid dosage form comprises about 9.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[63] In some embodiments, the solid dosage form comprises about 12.8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms). [64] In some embodiments, the solid dosage form comprises about 16 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a solid dosage form or plurality of solid dosage forms).

[65] In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the enteric coating comprises HPMC. In some embodiments, the enteric coating comprises a polymethacrylate-based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P).

[66] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules are administered, e.g., once or twice daily to a subject.

[67] In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Prevotella bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[68] In some embodiments, the capsule comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[69] In some embodiments, the capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[70] In some embodiments, the capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[71] In some embodiments, the capsule comprises about 6.4 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[72] In some embodiments, the capsule comprises about 8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[73] In some embodiments, the capsule comprises about 9.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[74] In some embodiments, the capsule comprises about 12.8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules). [75] In some embodiments, the capsule comprises about 16 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a capsule or plurality of capsules).

[76] In some embodiments, each capsule comprises about 1.6 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[77] In some embodiments, each capsule comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 8 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. [78] In some embodiments, each capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[79] In some embodiments, each capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 3.2 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. [80] In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the tablet is from 5mm to 18mm in diameter. In some embodiments, the enteric coating comprises HPMC. In some embodiments, the enteric coating comprises a polymethacrylate-based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P).

[81] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets are administered, e.g., once or twice daily to a subject.

[82] In some embodiments, the Prevotella bacteria in the tablet are lyophilized. In some embodiments, the Prevotella bacteria in the tablet are lyophilized (e.g., in a powder). In some embodiments, the Prevotella bacteria in the tablet are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[83] In some embodiments, the tablet comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[84] In some embodiments, the tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[85] In some embodiments, the tablet comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[86] In some embodiments, the tablet comprises about 6.4 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[87] In some embodiments, the tablet comprises about 8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[88] In some embodiments, the tablet comprises about 9.6 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[89] In some embodiments, the tablet comprises about 12.8 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets).

[90] In some embodiments, the tablet comprises about 16 x 10¹¹ total cells of the Prevotella bacteria (e.g., total dose of a tablet or plurality of tablets). [91] In some embodiments, each tablet comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 8 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[92] In some embodiments, each tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 1.6 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[93] In some embodiments, each tablet comprises about 3.2 x 10ⁿtotal cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 3.2 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[94] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini -tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., minitablets comprised in a capsule). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[95] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria.

[96] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹¹ total cells the Prevotella bacteria.

[97] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10¹¹ total cells the Prevotella bacteria.

[98] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹¹ total cells the Prevotella bacteria. [99] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹¹ total cells of the Prevotella bacteria.

[100] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10¹⁰to about 9.6 x IO¹⁰ total cells of the Prevotella bacteria.

[101] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 4.8 x 10¹⁰to about 9.6 x IO¹⁰ total cells of the Prevotella bacteria.

[102] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹⁰to about 9.6 x IO¹⁰ total cells of the Prevotella bacteria.

[103] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹⁰to about 8 x 10¹¹ total cells of the Prevotella bacteria.

[104] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹⁰to about 1.6 x 10¹¹ total cells of the Prevotella bacteria.

[105] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹⁰ to about 16 x 10¹¹ total cells of the Prevotella bacteria.

[106] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹⁰to about 8 x 10¹¹ total cells of the Prevotella bacteria.

[107] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹¹ to about 6.4 x 10¹¹ total cells of the Prevotella bacteria.

[108] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹¹ to about 8 x 10¹¹ total cells of the Prevotella bacteria.

[109] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹¹ to about 6.4 x 10¹¹ total cells of the Prevotella bacteria. [HO] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹⁰to about 8 x 10¹¹ total cells of the Prevotella bacteria.

[Hl] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[112] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[113] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[114] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[115] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[116] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[117] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[118] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[119] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[120] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ to about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[121] In some embodiments, the bacterial composition (e.g., prepared as a solid dosage form) (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[122] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.

[123] In some embodiments, the solid dosage form comprises about 8 x 10¹⁰to about 3.2 x 10¹¹ cells per solid dosage form.

[124] In some embodiments, the solid dosage form comprises about 3.2 x 10¹⁰to about 9.6 x IO¹⁰ cells per solid dosage form.

[125] In some embodiments, the solid dosage form comprises about 4.8 x 10¹⁰to about 9.6 x IO¹⁰ cells per solid dosage form.

[126] In some embodiments, the solid dosage form comprises about 6.4 x 10¹⁰to about 9.6 x IO¹⁰ cells per solid dosage form.

[127] In some embodiments, the solid dosage form comprises about 1.6xlO¹⁰ cells per solid dosage form.

[128] In some embodiments, the solid dosage form comprises about 8xlO¹⁰ cells per solid dosage form.

[129] In some embodiments, the solid dosage form comprises about 1.6xlOⁿ cells per solid dosage form.

[130] In some embodiments, the solid dosage form comprises about 3.2xlOⁿ cells per solid dosage form.

[131] In some embodiments, one solid dosage form is administered to the subject once daily.

[132] In some embodiments, one solid dosage form is administered to the subject twice daily.

[133] In some embodiments, two solid dosage forms are administered to the subject once daily.

[134] In some embodiments, two solid dosage forms are administered to the subject twice daily. [135] In some embodiments, three solid dosage forms are administered to the subject once daily.

[136] In some embodiments, three solid dosage forms are administered to the subject twice daily.

[137] In some embodiments, four solid dosage forms are administered to the subject once daily.

[138] In some embodiments, four solid dosage forms are administered to the subject twice daily.

[139] In some embodiments, five solid dosage forms are administered to the subject once daily.

[140] In some embodiments, five solid dosage forms are administered to the subject twice daily.

[141] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹⁰total cells.

[142] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells.

[143] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells.

[144] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10ⁿtotal cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. For clarity, about 3.2 x 10¹¹ total cells includes total cell counts within ±5% of 3.2 x 10¹¹ total cells e.g., 3.35 x 10¹¹ total cells.

[145] In some embodiments, the solid dosage form is a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 18mm in diameter. In some embodiments, the tablet comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[146] In some embodiments, the solid dosage form is a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the capsule (e.g., enteric coated capsule) is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule. In some embodiments, the capsule comprises about 1.6 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the capsule are lyophilized.

[147] In some embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a mini-tablet, e.g., an enteric coated mini-tablet. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, the enteric coating comprises a polymethacrylate-based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P or Eudragit L30-D55). [148] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella bacteria is prepared as a powder. The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises a powder comprising Prevotella bacteria. In some embodiments, the powder comprising Prevotella bacteria (e.g., at a dose provided herein) is resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage, or a food), e.g., for use in the methods provided herein.

[149] In some embodiments, the Prevotella histicola strain is administered in a bacterial composition (e.g., pharmaceutical composition) (e.g., a pharmaceutical composition provided herein). In some embodiments the bacterial composition (e.g., pharmaceutical composition) is a solid dose form provided herein. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises a blend of freeze- dried powder of Prevotella histicola and excipients (e.g. an encapsulated freeze-dried powder of a Prevotella histicola strain provided herein and excipients). In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises freeze-dried (e.g., lyophilized) powder of bacteria in a capsule. In some embodiments, the capsule is enteric coated. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises an enteric coated hydroxylpropyl methylcellulose (HPMC) hard capsule. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises a formulation of Prevotella histicola Strain B comprising freeze-dried powder of Prevotella histicola and excipients. In some embodiments, the excipients include mannitol, magnesium stearate and colloidal silicon dioxide. In some embodiments, each capsule contains about 8.0 x 1O¹⁰ cells of a. Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to a subject once daily. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to a subject twice daily. In some embodiments, 2 powder-containing capsules are administered to the subject daily. In some embodiments, 1 powder-containing capsule is administered to the subject daily. In some embodiments, each powder-containing capsule contains about 8.0 x io¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B). In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 powder-containing capsules are administered to a subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 4 powder-containing enteric coated capsules (e.g., each containing about 8.0 x io¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject once daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject twice daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject twice daily (e.g., for 1-7 days, 3 days, 7 days, 10 days, or 14 days), and then 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject once daily, e.g., for the duration of the treatment period (e.g., up to 14 days of total treatment). In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 8.0 x io¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject daily.

[150] In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject daily. In some embodiments, 1 powder-containing enteric coated capsules (e.g., containing about 8.0 x io¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject once daily. In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) is administered to the subject twice daily.

[151] In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x io¹⁰ cells of a Prevotella histicola strain provided herein (e.g., Prevotella histicola Strain B)) are administered to the subject once daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 8.0 x 1O¹⁰ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject twice daily.

[152] In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 3.2 x 10¹¹ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject daily. In some embodiments, 1 powder-containing enteric coated capsules (e.g., containing about 3.2 x io¹¹ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject once daily. In some embodiments, 1 powder-containing enteric coated capsule (e.g., containing about 3.2 x 10¹¹ cells of a. Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) is administered to the subject twice daily.

[153] In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 3.2 x 10¹¹ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 3.2 x io¹¹ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject once daily. In some embodiments, 2 powder-containing enteric coated capsules (e.g., each containing about 3.2 x 10¹¹ cells of a Prevotella histicola strain provided herein e.g., Prevotella histicola Strain B)) are administered to the subject twice daily.

[154] In some embodiments, the bacterial composition comprising Pre votella bacteria is prepared as a solid dose form, such as a tablet, capsule, or a powder. The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the bacterial composition comprises a powder comprising Prevotella bacteria. In some embodiments, the powder comprising Prevotella bacteria (e.g., at a dose provided herein) is resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage, or a food), e.g., for use in the methods provided herein.

[155] In some embodiments, the bacterial composition is administered orally. In some embodiments, the administration to the subject is once daily. In some embodiments, the administration to the subject is twice daily.

[156] In some embodiments, the bacterial composition is administered once daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for at least 20 weeks. In some embodiments, the bacterial composition is administered once daily for at least 36 weeks. In some embodiments, the bacterial composition is administered once daily for at least 52 weeks.

[157] In some embodiments, the bacterial composition comprises lyophilized Pre votella bacteria, e.g., in a powder. In some embodiments, the lyophilized Prevotella bacteria is formulated into a solid dose form, such as a tablet or capsule. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[158] In some embodiments, the bacterial composition is formulated as a tablet. In some embodiments, the bacterial formulation (e.g., composition) comprises an enteric coating or micro encapsulation.

[159] In some embodiments, the bacterial composition is formulated as a capsule. In some embodiments, the bacterial formulation (e.g., composition) comprises an enteric coating or micro encapsulation.

[160] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal (e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee).

[161] In some aspects, the disclosure provides use of a. Prevotella histicola strain provided herein and/or a bacterial composition (e.g., a bacterial composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for the preparation of a medicament for the performance of a therapeutic method provided herein. [162] In some aspects, the disclosure provides a Prevotella histicola strain provided herein and/or a bacterial composition (e.g., a bacterial composition and/or a solid dosage form) described herein (e.g., in an amount described herein) for use in the performance of a therapeutic method provided herein.

[163] In some embodiments, provided herein are methods of treating a subject who has a Thl mediated inflammatory disease comprising administering to the subject a bacterial composition described herein.

[164] In some embodiments, provided herein is a method of treating a Thl mediated inflammatory disease comprising administering (e.g., orally administering) to a human subject (e.g., a subject with a Thl mediated inflammatory disease) a strain of a Prevotella histicola and/or a composition (e.g, a bacterial composition (e.g., pharmaceutical composition) and/or a solid dosage form) comprising a strain of a. Prevotella histicola provided herein.

[165] In some embodiments, provided herein are methods of treating a subject who has a Th2 mediated inflammatory disease (such as asthma or atopic dermatitis) comprising administering to the subject a bacterial composition described herein.

[166] In some embodiments, provided herein is a method of treating a Th2 mediated inflammatory disease (such as asthma or atopic dermatitis) comprising administering (e.g, orally administering) to a human subject (e.g., a subject with a Th2 mediated inflammatory disease (such as asthma or atopic dermatitis)) a strain of a Prevotella histicola and/or a composition (e.g., a bacterial composition (e.g., pharmaceutical composition) and/or a solid dosage form) comprising a strain of a Prevotella histicola provided herein.

[167] In some embodiments, provided herein are methods of treating a subject who has a Thl7 mediated inflammatory disease (such as psoriasis) comprising administering to the subject a bacterial composition described herein.

[168] In some embodiments, provided herein is a method of treating a Thl7 mediated inflammatory disease (such as psoriasis) comprising administering (e.g., orally administering) to a human subject (e.g., a subject with a Thl7 mediated inflammatory disease (such as psoriasis)) a strain of a Prevotella histicola and/or a composition (e.g., a bacterial composition (e.g., pharmaceutical composition) and/or a solid dosage form) comprising a strain of a Prevotella histicola provided herein.

[169] In some embodiments, provided herein are methods of treating a subject who has psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) comprising administering to the subject a bacterial composition (e.g., pharmaceutical composition) described herein.

[170] In some embodiments, provided herein are methods of decreasing Lesion Severity Score (LSS) (e.g., mean LSS) (e.g., as compared to baseline or placebo control) in a subject (e.g., a subject with psoriasis) comprising administering to the subject a bacterial composition described herein. In some embodiments, the LSS in the subject is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more (e.g., by week 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 of treatment). In some embodiments, the LSS in the subject is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more after dosing is stopped (e.g., 24 weeks after treatment has stopped).

[171] In some embodiments, provided herein are methods of decreasing Psoriasis Area and Severity Index (PASI) score (e.g., mean PASI score) (e.g., as compared to baseline or placebo control) in a subject (e.g., a subject with psoriasis) comprising administering to the subject a bacterial composition described herein. In some embodiments, the PASI score in the subject is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more (e.g., by week 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 of treatment). In some embodiments, the PASI score in the subject is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more after dosing is stopped (e.g., 24 weeks after treatment has stopped).

[172] In some embodiments, provided herein are methods of increasing a sustained clinical effect (e.g., continued reductions from baseline (or placebo) in mean LSS and/or PASI (e.g., as compared to baseline or placebo control), e.g., 24 or more weeks after completion of dosing) in a subject (e.g., a subject with psoriasis) comprising administering to the subject a bacterial composition described herein. In some embodiments, the LSS and/or PASI score in the subject is reduced by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, or more (e.g., by week 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 of treatment).

[173] In some embodiments, provided herein are methods of enhancing anti-inflammatory cytokine production (e.g., increasing as compared to amount produced (e.g., mRNA and/or protein) in the absence of the bacterial composition) in a subject, the method comprising administering a bacterial composition described herein. In some embodiments, the antiinflammatory cytokine is IL-10, IL-27, and/or IL1RA. In some embodiments, the anti- inflammatory cytokine is expressed by Ml -type APCs. In some embodiments, enhancing anti-inflammatory cytokine production comprises an increase in anti-inflammatory cytokine (e.g., IL-10, IL-27, and/or IL1RA) mRNA levels (e.g., in skin biopsies). In some embodiments, enhancing anti-inflammatory cytokine production comprises an increase in anti-inflammatory cytokine (e.g., IL-10, IL-27, and/or IL1RA) protein levels (e.g., in blood samples).

[174] In some embodiments, provided herein are methods of inhibiting pro-inflammatory cytokine production (e.g., decreasing as compared to amount produced (e.g., mRNA and/or protein) in the absence of the bacterial composition) in a subject, the method comprising administering a bacterial composition described herein. In some embodiments, the pro- inflammatory cytokine is GM-CSF, IL-17A, and/or IL-13. In some embodiments, the pro- inflammatory cytokine is IL-6, TNF, and/or IL-12p70. In some embodiments, the pro- inflammatory cytokine is IL-23p40, IL- 17, IL-6, TNF, and/or IL-13. In some embodiments, the pro-inflammatory cytokine is IL-31, IL-23p40, IL-17, and/or IL-13. In some embodiments, the pro-inflammatory cytokine is IL-4, IL-5, and/or IL-13. In some embodiments, inhibiting pro-inflammatory cytokine production comprises inhibiting pro- inflammatory cytokine production in a draining lymph node (e.g., cervical lymph node). In some embodiments, inhibiting pro-inflammatory cytokine production comprises inhibiting pro-inflammatory cytokine production in the spleen. In some embodiments, inhibiting pro- inflammatory cytokine production comprises a decrease in pro-inflammatory cytokine (e.g., 1117a) mRNA levels (e.g., in skin biopsies). In some embodiments, inhibiting pro- inflammatory cytokine production comprises a decrease in pro-inflammatory cytokine (e.g., IL-17A) protein levels (e.g., in blood samples).

[175] In some embodiments, provided herein are methods of inhibiting pro-inflammatory chemokines production (e.g., decreasing as compared to amount produced (e.g., mRNA and/or protein) in the absence of the bacterial composition) in a subject, the method comprising administering a bacterial composition described herein. In some embodiments, the pro-inflammatory chemokine is keratinocyte chemoattractant (KC).

[176] In some embodiments, provided herein are methods of altering cytokine production or chemokine production (e.g., altering as compared to amount produced (e.g., mRNA and/or protein) in the absence of the bacterial composition) in a subject, the method comprising administering a bacterial composition described herein. In some embodiments, blood samples from the subject are stimulated ex vivo and analyzed for levels of cytokines and/or chemokines. In some embodiments, the level of IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL- 10, IL-12p40, IL-17A, TNFa, and/or IFNy is analyzed.

[177] In some embodiments, provided herein is a method of treating psoriasis comprising administering (e.g., orally administering) to a human subject a strain of a Prevotella histicola and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola provided herein. In some embodiments, the human subject has a confirmed diagnosis of mild to moderate plaque-type psoriasis for at least 6 months involving no more than 10% of body surface area (BSA) (excluding the scalp). In some embodiments, the human subject has a minimum of 2 psoriatic lesions. In some embodiments, the subject has not received systemic non-biologic psoriasis therapy (methotrexate [MTX], steroids, cyclophosphamide) or psoralen plus ultraviolet A (PUVA)/ultraviolet A (UVA) phototherapy within 4 weeks prior to dosing. In some embodiments, subject has not received treatment with biologic agents within 12 months prior to first dose. In some embodiments, the subject is not continuing use of topical or oral pharmacologically active agents 2 weeks prior to the start of dosing. In some embodiments, the human subject has a documented diagnosis of plaque psoriasis for >6 months. In some embodiments, the psoriasis comprises mild psoriasis. In some embodiments, the psoriasis comprises moderate psoriasis. In some embodiments, the psoriasis comprises severe psoriasis.

[178] In some embodiments, the human subject has had mild to moderate plaque psoriasis with plaque covering BSA of >3% and <10% and meet both of the following additional criteria: (i) PASI score of >6 and <15, and (ii) PGA score of 2 or 3.

[179] In some embodiments, the method decreases the PASI (Psoriasis Area and Severity Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PASI score prior to the commencement of treatment).

[180] In some embodiments, the method increases a PASI percentage response rate (e.g., PASI-50, PASI-75, PASI-90, or PASI-100), e.g., as described herein. For example, the percentage of subjects who achieve a 75% or greater reduction in PASI score from baseline is represented by the PASI-75 value, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment.

[181] In some embodiments, the method decreases the LSS (Lesion Severity Score) in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s LSS prior to the commencement of treatment), e.g., as described herein.

[182] In some embodiments, the method decreases the PGA (Physician’s Global Assessment) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PGA score prior to the commencement of treatment), e.g., as described herein.

[183] In some embodiments, the method decreases the percent of BSA (Body Surface Area) involvement in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s percent involvement prior to the commencement of treatment), e.g., as described herein.

[184] In some embodiments, the method decreases the mNAPSI (Modified Nail Psoriasis Severity Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s mNAPSI score prior to the commencement of treatment), e.g., as described herein.

[185] In some embodiments, the method improves (e.g., decreases) the DLQI (Dermatology Life Quality Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s DLQI score prior to the commencement of treatment), e.g., as described herein.

[186] In some embodiments, the method improves the product of PGA and BSA in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s product of PGA and BSA prior to the commencement of treatment), e.g., as described herein.

[187] In some embodiments, the method improves (e.g., decreases) the PSI (Psoriasis Symptom Inventory) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PSI score prior to the commencement of treatment), e.g., as described herein.

[188] In some embodiments, the method decreases pain in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s pain prior to the commencement of treatment), e.g., as described herein. For example, pain can be assessed by the SF-36 Bodily Pain Scale (SF-36 BPS) or the VAS Pain.

[189] In some embodiments, the method decreases fatigue in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s fatigue prior to the commencement of treatment), e.g., as described herein. [190] In some embodiments, provided herein are methods of treating a subject who has atopic dermatitis (e.g, mild to moderate atopic dermatitits, or mild, moderate, or severe atopic dermatitis) comprising administering to the subject a bacterial composition described herein.

[191] In some embodiments, provided herein is a method of treating atopic dermatitis comprising administering (e.g, orally administering) to a human subject a strain of a Prevotella histicola and/or a composition (e.g., a pharmaceutical composition and/or a solid dosage form) comprising a strain of Prevotella histicola. In some embodiments, the human subject has a confirmed diagnosis of mild to moderate atopic dermatitis for at least 6 months involving a minimum of 3% to a maximum of 15% body surface area. In some embodiments, the subject has had a confirmed diagnosis of mild to moderate atopic dermatitis with an IGA score of 2 or 3. In some embodiments, the human subject has moderate atopic dermatitis with a minimum of 5% and a maximum of 40% BSA involvement, and an IGA score of 2 or 3. In some embodiments, the human subject has severe atopic dermatitis. In some embodiments, the subject has at least 2 atopic dermatitis lesions with at least 1 in a site suitable for biopsy. In some embodiments, the subject is not receiving systemic non-biologic atopic dermatitis therapy (methotrexate (MTX), steroids, cyclophosphamide, or has received therapy within 4 weeks prior to dosing. In some embodiments, wherein the human subject is not receiving treatment with biologic agents within 12 months prior to first dose. In some embodiments, wherein the human subject is not continuing to use topical or oral pharmacologically active agents 2 weeks prior to the start of dosing. In some embodiments, the atopic dermatitis comprises mild atopic dermatitis. In some embodiments, the atopic dermatitis comprises moderate atopic dermatitis. In some embodiments, the atopic dermatitis comprises mild to moderate atopic dermatitis.

[192] In some embodiments, the method decreases the EASI (Eczema Area and Severity Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s EASI score prior to the commencement of treatment), e.g., as described herein. For example, the percentage of subjects achieving EASI-50; EASI-75; or EASI-90.

[193] In some embodiments, the method decreases the SCORAD (SCORing Atopic Dermatitis) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s SCORAD score prior to the commencement of treatment), e.g., as described herein. For example, the percentage of subjects achieving SCORAD-50 or SCORAD-75.

[194] In some embodiments, the method decreases the IGA (Investigator’s Global Assessment) (v-IGA) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s IGA score prior to the commencement of treatment), e.g., as described herein. For example, the percentage of subjects achieving an IGA score or 0 or 1.

[195] In some embodiments, the method decreases the Percentage of Body Surface Area (BSA) affected by disease in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s BSA percentage prior to the commencement of treatment), e.g., as described herein. For example, the percentage of subjects achieving BSA-50 or BSA-75; or the percentage of subjects achieving BSA reduction to 3% BSA or less.

[196] In some embodiments, the method improves the product of IGA and BSA in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s IGA x BSA prior to the commencement of treatment), e.g., as described herein.

[197] In some embodiments, the method improves the Dermatology Life Quality Index (DLQI) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s DLQI score prior to the commencement of treatment), e.g., as described herein.

[198] In some embodiments, the method improves the Patient-Oriented Eczema Measure (POEM) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s POEM score prior to the commencement of treatment), e.g., as described herein.

[199] In some embodiments, the method improves the Pruritus Numerical Rating Scale (Pruritus NRS (e.g., Peak Pruritus Numerical Rating Scale (PP-NRS))) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s Pruritus NRS score prior to the commencement of treatment), e.g., as described herein.

[200] In some embodiments, the method improves the number of courses or days of rescue therapy in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s SD-NRS score prior to the commencement of treatment), e.g., as described herein.

[201] In some embodiments, the method improves the Sleep Disturbance Numerical Rating Scale (SD-NRS) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s number of courses or days of rescue therapy) prior to the commencement of treatment), e.g., as described herein.

[202] In some embodiments, the method improves an AD rating scale score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s AD rating scale score prior to the commencement of treatment), e.g., as described herein. In some embodiments, the AD rating scale score comprises IGA, (e.g., vIGA), EASI, BSA, IGAxBSA, and/or SCORAD.

[203] In some embodiments, the method improves patient reported clinical rating scale score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s patient reported clinical rating scale score prior to the commencement of treatment), e.g., as described herein. In some embodiments, the patient reported clinical rating scale score comprises POEM, DLQI, ADCT, PP-NRS and/or SD- NRS.

[204] In some embodiments, the method improves the blood eosinophils in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s blood eosinophils prior to the commencement of treatment), e.g., as described herein.

[205] In some embodiments, the method improves the Sleep Disturbance Numerical Rating Scale (SD-NRS) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s number of courses or days of rescue therapy) prior to the commencement of treatment), e.g., as described herein.

[206] In some embodiments, the method decreases IgE levels in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s IgE levels prior to the commencement of treatment), e.g., as described herein.

[207] In some embodiments, the strain of a Prevotella histicola and/or a composition (e.g., a bacterial composition (e.g., pharmaceutical composition) and/or a solid dosage form) comprising a strain of a Prevotella histicola provided herein is administered with an additional therapy, wherein the additional therapy comprises an emollient. In some embodiments, the emollient is a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment. In some embodiments, the emollient is used at least daily. In some embodiments, the emollient is used at least twice daily.

[208] In some embodiments, provided herein are methods of treating a subject who has psoriatic arthritis comprising administering to the subject a bacterial composition described herein.

[209] In some embodiments, provided herein is a method of treating psoriatic arthritis comprising administering (e.g., orally administering) to a human subject (e.g., a subject with psoriatic arthritis) a strain of a Prevotella histicola and/or a composition (e.g., a bacterial composition (e.g., pharmaceutical composition) and/or a solid dosage form) comprising a strain of a Prevotella histicola provided herein. In some embodiments, the psoriatic arthritis comprises mild psoriatic arthritis. In some embodiments, the psoriatic arthritis comprises moderate psoriatic arthritis. In some embodiments, the psoriatic arthritis comprises severe psoriatic arthritis.

[210] In some embodiments, the method improves (e.g., increases) the percentage of subjects with an ACR20 response, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the percentage prior to the commencement of treatment), e.g., as described herein.

[211] In some embodiments, the method improves (e.g., increases) the percentage of subjects with an ACR50 response, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the percentage prior to the commencement of treatment), e.g., as described herein.

[212] In some embodiments, the method improves (e.g., increases) the percentage of subjects with an ACR70 response, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the percentage prior to the commencement of treatment), e.g., as described herein.

[213] In some embodiments, the method improves (e.g., increases) the Modified Psoriatic Arthritis Response Criteria (PsARC) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PsARC prior to the commencement of treatment), e.g., as described herein.

[214] In some embodiments, the method decreases the dactylitis severity score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s dactylitis severity score prior to the commencement of treatment), e.g., as described herein. [215] In some embodiments, the method decreases the Clinical Disease Activity Index (CD Al) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s CD Al prior to the commencement of treatment), e.g., as described herein.

[216] In some embodiments, the method decreases the DAS28 score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s DAS28 prior to the commencement of treatment), e.g., as described herein.

[217] In some embodiments, the method decreases the Maastricht Ankylosing Spondylitis Enthesis Score (MASES) in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s MASES prior to the commencement of treatment), e.g., as described herein.

[218] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating psoriasis (e.g., mild to moderate psoriasis).

[219] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating atopic dermatitis (e.g., mild to moderate atopic dermatitis).

[220] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating psoriatic arthritis.

[221] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of psoriasis (e.g., mild to moderate psoriasis).

[222] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of atopic dermatitis (e.g., mild, moderate, or severe atopic dermatitis).

[223] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of psoriatic arthritis.

[224] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating an inflammatory disease. In some embodiments, the inflammatory disease is a Thl, Th2, or Thl7 inflammatory disease.

[225] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating an immune disorder. [226] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of an inflammatory disease. In some embodiments, the inflammatory disease is a Thl, Th2, or Thl7 inflammatory disease.

[227] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of an immune disorder.

[228] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of an autoimmune disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of an autoimmune disease).

[229] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating an autoimmune disease.

[230] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of an inflammatory disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of an inflammatory disease).

[231] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating an inflammatory disease.

[232] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of a metabolic disease, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a metabolic disease).

[233] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating a metabolic disease.

[234] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of a dysbiosis, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a dysbiosis).

[235] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating a dysbiosis.

[236] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels), (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels)).

[237] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels).

[238] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for decreasing IgE levels (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for decreasing IgE levels).

[239] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in decreasing IgE levels.

[240] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for decreasing IL-31, IL-23p40, IL- 17, IL-4, IL-5, and/or IL- 13 levels (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for decreasing inflammatory cytokine expression (e.g., decreased IL-31, IL-23p40, IL-17, IL-4, IL-5, and/or IL- 13 levels)).

[241] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in decreasing IL-31, IL-23p40, IL-17, IL-4, IL- 5, and/or IL-13 levels.

[242] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of bacterial septic shock, cytokine storm and/or viral infection, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of bacterial septic shock, cytokine storm and/or viral infection).

[243] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating bacterial septic shock, cytokine storm and/or viral infection.

[244] In some aspects, the disclosure provides use of a bacterial composition described herein (e.g., in an amount described herein) for the preparation of a medicament for the treatment of a viral infection, (e.g., in a subject, e.g., a human subject) and methods of using such bacterial compositions (e.g., for the treatment of a viral infection). In some embodiments, the viral infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection. In some embodiments the viral infection is a SARS- CoV-2 infection.

[245] In some aspects, the disclosure provides a bacterial composition described herein (e.g., in an amount described herein) for use in treating a viral infection. In some embodiments, the viral infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection. In some embodiments the viral infection is a SARS- CoV-2 infection.

[246] In some embodiments, provided herein are methods of decreasing inflammation in a subject (e.g., a subject who has psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) and/or atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis)) and/or psoriatic arthritis (e.g., mild, moderate, or severe psoriatic arthritis) comprising administering to the subject a bacterial composition described herein, wherein the effects on inflammation of the administration of the bacterial composition persist for at least 24 weeks after last dosing the subject (e.g., the level of inflammation is lower 24 weeks after last dosing the subject, as compared to the level of inflammation prior to commencement of dosing the subject ). Persistence can be determined by the decrease in the level of inflammation being greater at 24 weeks after last dosing the subject than the level of inflammation prior to commencement of dosing the subject.

[247] In some aspects, the disclosure provides a method of treating psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[248] In some aspects, the disclosure provides a method of treating psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[249] In some aspects, the disclosure provides a method of treating psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 8 x IO¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[250] In some aspects, the disclosure provides a method of treating psoriasis (e.g., mild to moderate psoriasis, or mild, moderate, or severe psoriasis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[251] In some aspects, the disclosure provides a method of treating atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[252] In some aspects, the disclosure provides a method of treating atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[253] In some aspects, the disclosure provides a method of treating atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 8 x IO¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[254] In some aspects, the disclosure provides a method of treating atopic dermatitis (e.g., mild to moderate atopic dermatitis, or mild, moderate, or severe atopic dermatitis) in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[255] In some aspects, the disclosure provides a method of reducing inflammation in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[256] In some aspects, the disclosure provides a method of reducing inflammation in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[257] In some aspects, the disclosure provides a method of reducing inflammation in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in one solid dosage form (e.g., tablet or capsule) and comprises about 8 x 10¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. [258] In some aspects, the disclosure provides a method of reducing inflammation in a human subject comprising orally administering (e.g., once or twice daily) to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is formulated in two solid dosage forms (e.g., tablets or capsules) and each solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria. In some embodiments, the dose is administered for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[259] In some embodiments, the inflammation comprises Thl inflammation.

[260] In some embodiments, the inflammation comprises Th2 inflammation.

[261] In some embodiments, the inflammation comprises Thl inflammation.

DETAILED DESCRIPTION

[262] Prevotella histicola is a natural human commensal organism, commonly found on oral, nasopharyngeal, gastrointestinal (GI), and genito-urinary mucosal surfaces. Preclinical studies using Prevotella histicola Strain B have been carried out across a range of human and mouse primary cell in vitro assays, which support the use of this agent in the treatment of psoriasis, atopic dermatitis, and psoriatic arthritis. As described herein, Prevotella histicola Strain B can be used for at least 20 weeks.

[263] In some aspects, described herein is an oral therapy for treating an inflammatory disease with Prevotella histicola Strain B. In some embodiments, the inflammatory disease is a Thl, Th2, or Thl7 inflammatory disease.

[264] In some aspects, described herein is an oral therapy for treating an immune disorder with Prevotella histicola Strain B.

[265] In some aspects, described herein is an oral therapy for treating psoriasis with Prevotella histicola Strain B.

[266] In some aspects, described herein is an oral therapy for treating atopic dermatitis with Prevotella histicola Strain B.

[267] In some aspects, described herein is an oral therapy for treating psoriatic arthritis with Prevotella histicola Strain B.

[268] In some aspects, described herein is an oral therapy for treating an autoimmune disease with Prevotella histicola Strain B.

[269] In some aspects, described herein is an oral therapy for treating a metabolic disease with Prevotella histicola Strain B. [270] In some aspects, described herein is an oral therapy for treating a dysbiosis with Prevotella histicola Strain B.

[271] In some aspects, described herein is an oral therapy for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels with Prevotella histicola Strain B.

[272] In some aspects, described herein is an oral therapy for decreasing IgE levels with Prevotella histicola Strain B.

[273] In some aspects, described herein is an oral therapy for treating bacterial septic shock with Prevotella histicola Strain B.

[274] In some aspects, described herein is an oral therapy for treating a viral infection with Prevotella histicola Strain B.

[275] In some aspects, described herein is an oral therapy for treating a cytokine storm with Prevotella histicola Strain B.

Definitions

[276] The term “about” when used before a numerical value indicates that the value may vary within a reasonable range, such as within ±10%, ±5% or ±1% of the stated value.

[277] “Adjuvant” or “Adjuvant therapy” broadly refers to an agent that affects an immunological or physiological response in a patient or subject. For example, an adjuvant might increase the presence of an antigen over time or help absorb an antigen presenting cell antigen, activate macrophages and lymphocytes and support the production of cytokines. By changing an immune response, an adjuvant might permit a smaller dose of an immune interacting agent to increase the effectiveness or safety of a particular dose of the immune interacting agent. For example, an adjuvant might prevent T cell exhaustion and thus increase the effectiveness or safety of a particular immune interacting agent.

[278] “Administration” broadly refers to a route of administration of a composition to a subject. Examples of routes of administration include oral administration, rectal administration, topical administration, inhalation (nasal) or injection. Administration by injection includes intravenous (IV), intramuscular (IM), and subcutaneous (SC) administration. The bacterial compositions described herein can be administered in any form by any effective route, including but not limited to oral, parenteral, enteral, intravenous, intraperitoneal, topical, transdermal (e.g., using any standard patch), intradermal, ophthalmic, (intra)nasally, local, non-oral, such as aerosol, inhalation, subcutaneous, intramuscular, buccal, sublingual, (trans)rectal, vaginal, intra-arterial, and intrathecal, transmucosal (e.g., sublingual, lingual, (trans)buccal, (trans)urethral, vaginal (e.g., trans- and perivaginally), implanted, intravesical, intrapulmonary, intraduodenal, intragastrical, and intrabronchial. In some embodiments, the bacterial compositions described herein are administered orally, rectally, topically, intravesically, by injection into or adjacent to a draining lymph node, intravenously, by inhalation or aerosol, or subcutaneously. In some embodiments, the bacterial compositions described herein are administered orally.

[279] “ Cellular augmentation” broadly refers to the influx of cells or expansion of cells in an environment that are not substantially present in the environment prior to administration of a composition and not present in the composition itself. Cells that augment the environment include immune cells, stromal cells, bacterial and fungal cells.

[280] “ Clade” refers to the OTUs or members of a phylogenetic tree that are downstream of a statistically valid node in a phylogenetic tree. The clade comprises a set of terminal leaves in the phylogenetic tree that is a distinct monophyletic evolutionary unit and that share some extent of sequence similarity. “Operational taxonomic units,” “OTU” (or plural, “OTUs”) refer to a terminal leaf in a phylogenetic tree and is defined by a nucleic acid sequence, e.g., the entire genome, or a specific genetic sequence, and all sequences that share sequence identity to this nucleic acid sequence at the level of species. In some embodiments the specific genetic sequence may be the 16S sequence or a portion of the 16S sequence. In other embodiments, the entire genomes of two entities are sequenced and compared. In another embodiment, select regions such as multilocus sequence tags (MLST), specific genes, or sets of genes may be genetically compared. In 16S embodiments, OTUs that share ^97% average nucleotide identity across the entire 16S or some variable region of the 16S are considered the same OTU (see e.g. Claesson M J, Wang Q, O'Sullivan O, Greene-Diniz R, Cole J R, Ros R P, and O'Toole P W. 2010. Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res 38: e200. Konstantinidis K T, Ramette A, and Tiedje J M. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361 : 1929-1940.). In embodiments involving the complete genome, MLSTs, specific genes, or sets of genes OTUs that share ^95% average nucleotide identity are considered the same OTU (see e.g. Achtman M, and Wagner M. 2008. Microbial diversity and the genetic nature of microbial species. Nat. Rev. Microbiol. 6: 431-440. Konstantinidis K T, Ramette A, and Tiedje J M. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361 : 1929-1940.). OTUs are frequently defined by comparing sequences between organisms. Generally, sequences with less than 95% sequence identity are not considered to form part of the same OTU. OTUs may also be characterized by any combination of nucleotide markers or genes, in particular highly conserved genes (e.g., “house-keeping” genes), or a combination thereof. Such characterization employs, e.g., WGS data or a whole genome sequence.

[281] A “combination” of two or more monoclonal microbial strains includes the physical co-existence of the two monoclonal microbial strains, either in the same material or product or in physically connected products, as well as the temporal co-admini strati on or colocalization of the monoclonal microbial strains.

[282] The term “decrease” or “deplete” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 1/100, 1/1000, 1/10,000, 1/100,000, 1/1,000,000 or undetectable after treatment when compared to a pre-treatment state. Properties that may be decreased include the number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size (e.g., in an animal tumor model)).

[283] “Dysbiosis” refers to a state of the microbiota or microbiome of the gut or other body area, including, e.g., mucosal or skin surfaces (or any other microbiome niche) in which the normal diversity and/or function of the host gut microbiome ecological networks “microbiome”) are disrupted. A state of dysbiosis may result in a diseased state, or it may be unhealthy under only certain conditions or only if present for a prolonged period. Dysbiosis may be due to a variety of factors, including, environmental factors, infectious agents, host genotype, host diet and/or stress. A dysbiosis may result in: a change (e.g., increase or decrease) in the prevalence of one or more bacteria types (e.g., anaerobic), species and/or strains, change (e.g., increase or decrease) in diversity of the host microbiome population composition; a change (e.g., increase or reduction) of one or more populations of symbiont organisms resulting in a reduction or loss of one or more beneficial effects; overgrowth of one or more populations of pathogens (e.g., pathogenic bacteria); and/or the presence of, and/or overgrowth of, symbiotic organisms that cause disease only when certain conditions are present. [284] As used herein, “engineered bacteria” are any bacteria that have been genetically altered from their natural state by human intervention and the progeny of any such bacteria. Engineered bacteria include, for example, the products of targeted genetic modification, the products of random mutagenesis screens and the products of directed evolution.

[285] The term “epitope” means a protein determinant capable of specific binding to an antibody or T cell receptor. Epitopes usually consist of chemically active surface groupings of molecules such as amino acids or sugar side chains. Certain epitopes can be defined by a particular sequence of amino acids to which an antibody is capable of binding.

[286] The term “gene” is used broadly to refer to any nucleic acid associated with a biological function. The term “gene” applies to a specific genomic sequence, as well as to a cDNA or an mRNA encoded by that genomic sequence.

[287] “Identity” as between nucleic acid sequences of two nucleic acid molecules can be determined as a percentage of identity using known computer algorithms such as the “FASTA” program, using for example, the default parameters as in Pearson et al. (1988) Proc. Natl. Acad. Sci. USA 85:2444 (other programs include the GCG program package (Devereux, J., et al., Nucleic Acids Research 12(I):387 (1984)), BLASTP, BLASTN, FASTA Atschul, S. F., et al., J Molec Biol 215:403 (1990); Guide to Huge Computers, Martin J. Bishop, ed., Academic Press, San Diego, 1994, and Carillo et al. (1988) SIAM J Applied Math 48: 1073). For example, the BLAST function of the National Center for Biotechnology Information database can be used to determine identity. Other commercially or publicly available programs include, DNAStar “MegAlign” program (Madison, Wis.) and the University of Wisconsin Genetics Computer Group (UWG) “Gap” program (Madison Wis.)).

[288] As used herein, the term “immune disorder” refers to any disease, disorder or disease symptom caused by an activity of the immune system, including autoimmune diseases, inflammatory diseases and allergies. Immune disorders include, but are not limited to, autoimmune diseases (e.g., Lupus, Scleroderma, hemolytic anemia, vasculitis, type one diabetes, Grave’s disease, rheumatoid arthritis, multiple sclerosis, Goodpasture’s syndrome, pernicious anemia and/or myopathy), inflammatory diseases (e.g., acne vulgaris, asthma, celiac disease, chronic prostatitis, glomerulonephritis, inflammatory bowel disease, pelvic inflammatory disease, reperfusion injury, rheumatoid arthritis, sarcoidosis, transplant rejection, vasculitis and/or interstitial cystitis), and/or an allergies (e.g., food allergies, drug allergies and/or environmental allergies). [289] “Immunotherapy” is treatment that uses a subject’s immune system to treat disease (e.g., immune disease) and includes, for example, checkpoint inhibitors, cytokines, cell therapy, CAR-T cells, and dendritic cell therapy.

[290] The term “increase” means a change, such that the difference is, depending on circumstances, at least 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, 2-fold, 4-fold, 10-fold, 100-fold, 10^A3 fold, 10^A4 fold, 10^A5 fold, 10^A6 fold, and/or 10^A7 fold greater after treatment when compared to a pre-treatment state. Properties that may be increased include the number of immune cells, bacterial cells, stromal cells, myeloid derived suppressor cells, fibroblasts, metabolites; the level of a cytokine; or another physical parameter (such as ear thickness (e.g., in a DTH animal model) or tumor size (e.g., in an animal tumor model).

[291] “Innate immune agonists” or “immuno-adjuvants” are small molecules, proteins, or other agents that specifically target innate immune receptors including Toll-Like Receptors (TLR), NOD receptors, RLRs, C-type lectin receptors, STING-cGAS Pathway components, inflammasome complexes. For example, LPS is a TLR-4 agonist that is bacterially derived or synthesized and aluminum can be used as an immune stimulating adjuvant. Immuno- adjuvants are a specific class of broader adjuvant or adjuvant therapy. Examples of STING agonists include, but are not limited to, 2'3'- cGAMP, 3'3'-cGAMP, c-di-AMP, c-di-GMP, 2'2'-cGAMP, and 2'3'-cGAM(PS)2 (Rp/Sp) (Rp, Sp-isomers of the bis-phosphorothioate analog of 2'3'-cGAMP). Examples of TLR agonists include, but are not limited to, TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR1O and TLRI 1. Examples of NOD agonists include, but are not limited to, N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyldipeptide (MDP)), gamma-D-glutamyl-meso-diaminopimelic acid (iE-DAP), and desmuramylpeptides (DMP).

[292] The term “isolated” or “enriched” encompasses a microbe, bacteria or other entity or substance that has been (1) separated from at least some of the components with which it was associated when initially produced (whether in nature or in an experimental setting), and/or (2) produced, prepared, purified, and/or manufactured by the hand of man. Isolated microbes may be separated from at least about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or more of the other components with which they were initially associated. In some embodiments, isolated microbes are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure, e.g., substantially free of other components. The terms “purify,” “purifying” and “purified” refer to a microbe or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g. , whether in nature or in an experimental setting), or during any time after its initial production. A microbe or a microbial population may be considered purified if it is isolated at or after production, such as from a material or environment containing the microbe or microbial population, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered “isolated.” In some embodiments, purified microbes or microbial population are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. In the instance of microbial compositions provided herein, the one or more microbial types present in the composition can be independently purified from one or more other microbes produced and/or present in the material or environment containing the microbial type. Microbial compositions and the microbial components thereof are generally purified from residual habitat products.

[293] “Metabolite” as used herein refers to any and all molecular compounds, compositions, molecules, ions, co-factors, catalysts or nutrients used as substrates in any cellular or microbial metabolic reaction or resulting as product compounds, compositions, molecules, ions, co-factors, catalysts or nutrients from any cellular or microbial metabolic reaction.

[294] “Microbe” refers to any natural or engineered organism characterized as a bacterium, fungus, microscopic alga, protozoan, and the stages of development or life cycle stages e.g., vegetative, spore (including sporulation, dormancy, and germination), latent, biofilm) associated with the organism.

[295] “Microbiome” broadly refers to the microbes residing on or in body site of a subject or patient. Microbes in a microbiome may include bacteria, viruses, eukaryotic microorganisms, and/or viruses. Individual microbes in a microbiome may be metabolically active, dormant, latent, or exist as spores, may exist planktonically or in biofilms, or may be present in the microbiome in sustainable or transient manner. The microbiome may be a commensal or healthy-state microbiome or a disease-state microbiome. The microbiome may be native to the subject or patient, or components of the microbiome may be modulated, introduced, or depleted due to changes in health state or treatment conditions e.g., antibiotic treatment, exposure to different microbes). In some aspects, the microbiome occurs at a mucosal surface. In some aspects, the microbiome is a gut microbiome.

[296] A “microbiome profile” or a “microbiome signature” of a tissue or sample refers to an at least partial characterization of the bacterial makeup of a microbiome. In some embodiments, a microbiome profile indicates whether at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more bacterial strains are present or absent in a microbiome. In some embodiments, a microbiome profile indicates whether at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100 or more bacterial strains are present in a sample. In some embodiments, the microbiome profile indicates the relative or absolute amount of each bacterial strain detected in the sample.

[297] “Modified” in reference to a bacteria broadly refers to a bacteria that has undergone a change from its wild-type form. Examples of bacterial modifications include genetic modification, gene expression, phenotype modification, formulation, chemical modification, and dose or concentration. Examples of improved properties are described throughout this specification and include, e.g., attenuation, auxotrophy, homing, or antigenicity. Phenotype modification might include, by way of example, bacteria growth in media that modify the phenotype of a bacterium that increase or decrease virulence.

[298] As used herein, a gene is “overexpressed” in a bacteria if it is expressed at a higher level in an engineered bacteria under at least some conditions than it is expressed by a wildtype bacteria of the same species under the same conditions. Similarly, a gene is “underexpressed” in a bacteria if it is expressed at a lower level in an engineered bacteria under at least some conditions than it is expressed by a wild-type bacteria of the same species under the same conditions.

[299] The terms “polynucleotide”, and “nucleic acid” are used interchangeably. They refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides or ribonucleotides, or analogs thereof. Polynucleotides may have any three-dimensional structure, and may perform any function. The following are non-limiting examples of polynucleotides: coding or non-coding regions of a gene or gene fragment, loci (locus) defined from linkage analysis, exons, introns, messenger RNA (mRNA), micro RNA (miRNA), silencing RNA (siRNA), transfer RNA, ribosomal RNA, ribozymes, cDNA, recombinant polynucleotides, branched polynucleotides, plasmids, vectors, isolated DNA of any sequence, isolated RNA of any sequence, nucleic acid probes, and primers. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. If present, modifications to the nucleotide structure may be imparted before or after assembly of the polymer. A polynucleotide may be further modified, such as by conjugation with a labeling component. In all nucleic acid sequences provided herein, U nucleotides are interchangeable with T nucleotides.

[300] “Operational taxonomic units” and “OTU(s)” refer to a terminal leaf in a phylogenetic tree and is defined by a nucleic acid sequence, e.g., the entire genome, or a specific genetic sequence, and all sequences that share sequence identity to this nucleic acid sequence at the level of species. In some embodiments the specific genetic sequence may be the 16S sequence or a portion of the 16S sequence. In other embodiments, the entire genomes of two entities are sequenced and compared. In another embodiment, select regions such as multilocus sequence tags (MLST), specific genes, or sets of genes may be genetically compared. For 16S, OTUs that share > 97% average nucleotide identity across the entire 16S or some variable region of the 16S are considered the same OTU. See e.g. Claesson MJ, Wang Q, O’Sullivan O, Greene-Diniz R, Cole JR, Ross RP, and O’Toole PW. 2010. Comparison of two next-generation sequencing technologies for resolving highly complex microbiota composition using tandem variable 16S rRNA gene regions. Nucleic Acids Res 38: e200. Konstantinidis KT, Ramette A, and Tiedje JM. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361 : 1929-1940. For complete genomes, MLSTs, specific genes, other than 16S, or sets of genes OTUs that share > 95% average nucleotide identity are considered the same OTU. See e.g., Achtman M, and Wagner M. 2008. Microbial diversity and the genetic nature of microbial species. Nat. Rev. Microbiol. 6: 431-440. Konstantinidis KT, Ramette A, and Tiedje JM. 2006. The bacterial species definition in the genomic era. Philos Trans R Soc Lond B Biol Sci 361 : 1929-1940. OTUs are frequently defined by comparing sequences between organisms. Generally, sequences with less than 95% sequence identity are not considered to form part of the same OTU. OTUs may also be characterized by any combination of nucleotide markers or genes, in particular highly conserved genes (e.g., “house-keeping” genes), or a combination thereof. Operational Taxonomic Units (OTUs) with taxonomic assignments made to, e.g., genus, species, and phylogenetic clade are provided herein.

[301] As used herein, a substance is “pure” if it is substantially free of other components. The terms “purify,” “purifying” and “purified” refer to a microbe or other material that has been separated from at least some of the components with which it was associated either when initially produced or generated (e.g., whether in nature or in an experimental setting), or during any time after its initial production. A microbe may be considered purified if it is isolated at or after production, such as from one or more other bacterial components, and a purified microbe or microbial population may contain other materials up to about 10%, about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, or above about 90% and still be considered “purified.” In some embodiments, purified microbes are more than about 80%, about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or more than about 99% pure. Bacterial compositions and the microbial components thereof are, e.g., purified from residual habitat products.

[302] “Residual habitat products” refers to material derived from the habitat for microbiota within or on a subject. For example, microbes live in feces in the gastrointestinal tract, on the skin itself, in saliva, mucus of the respiratory tract, or secretions of the genitourinary tract (i.e., biological matter associated with the microbial community). Substantially free of residual habitat products means that the microbial composition no longer contains the biological matter associated with the microbial environment on or in the human or animal subject and is 100% free, 99% free, 98% free, 97% free, 96% free, or 95% free of any contaminating biological matter associated with the microbial community. Residual habitat products can include abiotic materials (including undigested food) or it can include unwanted microorganisms. Substantially free of residual habitat products may also mean that the microbial composition contains no detectable cells from a human or animal and that only microbial cells are detectable. In one embodiment, substantially free of residual habitat products may also mean that the microbial composition contains no detectable viral (including microbial viruses (e.g., phage)), fungal, mycoplasmal contaminants. In another embodiment, it means that fewer than 1x10-2%, 1x10-3%, 1x10- 4%, 1x10-5%, 1x10-6%, 1x10-7%, 1x10-8% of the viable cells in the microbial composition are human or animal, as compared to microbial cells. There are multiple ways to accomplish this degree of purity, none of which are limiting. Thus, contamination may be reduced by isolating desired constituents through multiple steps of streaking to single colonies on solid media until replicate (such as, but not limited to, two) streaks from serial single colonies have shown only a single colony morphology. Alternatively, reduction of contamination can be accomplished by multiple rounds of serial dilutions to single desired cells (e.g., a dilution of 10-8 or 10-9), such as through multiple 10-fold serial dilutions. This can further be confirmed by showing that multiple isolated colonies have similar cell shapes and Gram staining behavior. Other methods for confirming adequate purity include genetic analysis (e.g., PCR, DNA sequencing), serology and antigen analysis, enzymatic and metabolic analysis, and methods using instrumentation such as flow cytometry with reagents that distinguish desired constituents from contaminants.

[303] The terms “subject” or “patient” refers to any animal. A subject or a patient described as “in need thereof’ refers to one in need of a treatment for a disease. Mammals (z.e., mammalian animals) include humans, laboratory animals (e.g., primates, rats, mice), livestock (e.g., cows, sheep, goats, pigs), and household pets (e.g., dogs, cats, rodents). For example, the subject may be a non-human mammal including but not limited to of a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee.

[304] “ Strain” refers to a member of a bacterial species with a genetic signature such that it may be differentiated from closely-related members of the same bacterial species. The genetic signature may be the absence of all or part of at least one gene, the absence of all or part of at least on regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the absence (“curing”) of at least one native plasmid, the presence of at least one recombinant gene, the presence of at least one mutated gene, the presence of at least one foreign gene (a gene derived from another species), the presence at least one mutated regulatory region (e.g., a promoter, a terminator, a riboswitch, a ribosome binding site), the presence of at least one non-native plasmid, the presence of at least one antibiotic resistance cassette, or a combination thereof. Genetic signatures between different strains may be identified by PCR amplification optionally followed by DNA sequencing of the genomic region(s) of interest or of the whole genome. In the case in which one strain (compared with another of the same species) has gained or lost antibiotic resistance or gained or lost a biosynthetic capability (such as an auxotrophic strain), strains may be differentiated by selection or counter-selection using an antibiotic or nutrient/metabolite, respectively.

[305] As used herein, the term “treating” a disease in a subject or “treating” a subject having or suspected of having a disease refers to subjecting the subject to a pharmaceutical treatment, e.g., the administration of one or more agents, such that at least one symptom of the disease is decreased or prevented from worsening. Thus, in one embodiment, “treating” refers inter alia to delaying progression, expediting remission, inducing remission, augmenting remission, speeding recovery, increasing efficacy of or decreasing resistance to alternative therapeutics, or a combination thereof. The methods and compositions described herein can be used to treat any subject in need thereof. As used herein, a “subject in need thereof’ includes any subject that has the disease or disorder, as well as any subject with an increased likelihood of acquiring a such a disease or disorder.

Bacteria

[306] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) (e.g., solid dosage forms thereof) comprising Prevotella histicola useful for the treatment and/or prevention of inflammation (e.g., Thl, Th2, or Thl7 inflammation) and methods of using such bacterial compositions (e.g., for the treatment of inflammation (e.g., Thl, Th2, or Thl7 inflammation)), e.g., in a subject, e.g., in a human subject. In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). In some embodiments, the Prevotella histicola bacteria are non-live. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises only one strain of bacteria, e.g., Prevotella histicola.

[307] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) (e.g., solid dosage forms thereof) comprising Prevotella histicola useful for the treatment and/or prevention of psoriasis (e.g., mild to moderate psoriasis) and methods of using such bacterial compositions (e.g., for the treatment of psoriasis), e.g., in a subject, e.g., in a human subject. In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, attenuated bacteria). In some embodiments, the Prevotella histicola bacteria are non-live. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises only one strain of bacteria, e.g., Prevotella histicola.

[308] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) (e.g., solid dosage forms thereof) comprising Prevotella histicola useful for the treatment and/or prevention of atopic dermatitis (e.g., mild, moderate, or severe atopic dermatitis) and methods of using such bacterial compositions (e.g., for the treatment of atopic dermatitis), e.g., in a subject, e.g., in a human subject. In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, attenuated bacteria). In some embodiments, the Prevotella histicola bacteria are non-live. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises only one strain of bacteria, e.g., Prevotella histicola.

[309] In some aspects, provided herein are bacterial compositions (e.g., pharmaceutical compositions) (e.g., solid dosage forms thereof) comprising Prevotella histicola useful for the treatment and/or prevention of psoriatic arthritis and methods of using such bacterial compositions (e.g., for the treatment of psoriatic arthritis), e.g., in a subject, e.g., in a human subject. In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, attenuated bacteria). In some embodiments, the Prevotella histicola bacteria are non-live. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises only one strain of bacteria, e.g., Prevotella histicola.

[310] In some embodiments, the Prevotella histicola is Prevotella Strain B 50329 (NRRL accession number B 50329) (also referred to as “Prevotella histicola Strain B” or “Prevotella Strain B”). In some embodiments, the Prevotella strain is a strain comprising at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella Strain B 50329.

[311] Prevotella histicola Strain B can be cultured according to methods known in the art. For example, Prevotella histicola can be grown in ATCC Medium 2722, ATCC Medium 1490, or other medium using methods disclosed, for example in Caballero et al., 2017. “Cooperating Commensals Restore Colonization Resistance to Vancomycin-Resistant Enterococcus faecium” Cell Host & Microbe 21 : 592-602, which is hereby incorporated by reference in its entirety.

[312] In some embodiments, the Prevotella bacteria (e.g., in a bacterial composition) is quantified based on total cells, e.g., total cell count (TCC) (e.g., determined by Coulter counter).

[313] In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. [314] In some embodiments, the bacterial composition is administered twice daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered twice daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[315] In some embodiments, the bacterial composition is formulated as a solid dosage form, e.g., a capsule or a tablet. In some embodiments, the solid dosage form (e.g., of the composition) comprises an enteric coating or micro encapsulation. In some embodiments, the solid dosage form comprises a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the solid dosage form comprises a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coating allows release of the bacterial composition in the small intestine, e.g., in the upper small intestine, e.g., in the duodenum.

[316] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal (e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee).

Bacterial Compositions

[317] A “bacterial composition” of the present disclosure can be or include a pharmaceutical composition. A bacterial composition contains bacteria or a solution or dried form (for example, powder (such as a lyophilized powder or spray-dried powder) or lyophilate (for example, lyophilized powder or lyophilized cake)) that comprises bacteria. In some embodiments, the bacterial composition is a pharmaceutical composition. In some embodiments, the bacterial composition is (or is present in) a medicinal product, medical food, a food product, or a dietary supplement. In some embodiments, a bacterial composition provides a therapeutically effective amount of bacteria contained therein.

[318] In some embodiments, the methods provided herein comprise use of bacterial compositions (e.g., pharmaceutical compositions) comprising Prevotella histicola bacteria provided herein.

[319] In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, and/or attenuated bacteria). In some embodiments, the Prevotella histicola bacteria are non-viable (e.g., less than about 1% of the bacteria (e.g., of a composition) are viable). In some embodiments, the Prevotella histicola bacteria have been gamma irradiated (e.g., according to a method described herein). In some embodiments, the Prevotella histicola bacteria are live. In some embodiments, the Prevotella histicola bacteria are non-live (e.g., less than about 1% of the bacteria (e.g., of a composition) are live). For example, non-live bacteria do not form colonies when plated (e.g., do not have colony forming units (CFUs)) (e.g., when plated in conditions that allow growth) (e.g., less than about 1% of the bacteria (e.g., of a composition) form colonies when plated).

[320] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprises only one strain of bacteria, e.g., Prevotella histicola.

[321] In some embodiments, the Prevotella histicola is Prevotella Strain B 50329 (NRRL accession number B 50329). In some embodiments, the Prevotella strain is a strain comprising at least 85%, at least 86%, at least 87%, at least 88%, at least 89%, at least 90%, at least 91%, at least 92%, at least 93%, at least 94%, at least 95%, at least 96%, at least 97%, at least 98%, or at least 99% sequence identity (e.g., at least 99.5% sequence identity, at least 99.6% sequence identity, at least 99.7% sequence identity, at least 99.8% sequence identity, at least 99.9% sequence identity) to the nucleotide sequence (e.g., genomic sequence, 16S sequence, CRISPR sequence) of the Prevotella Strain B 50329.

[322] In some embodiments, the bacterial compositions comprise whole Prevotella histicola bacteria (e.g., live bacteria, non-live bacteria, killed bacteria, attenuated bacteria).

[323] In some embodiments, the bacterial composition is formulated as a capsule or a tablet. In some embodiments, the bacterial composition comprises an enteric coating or micro encapsulation. In some embodiments, the bacterial composition is prepared as a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the bacterial composition is prepared as a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coating allows release of the bacterial composition in the small intestine, e.g., in the upper small intestine, e.g., in the duodenum.

[324] In some embodiments, the bacterial composition comprises about 50 mg to about 3 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[325] In some embodiments, the bacterial composition comprises about 55mg, about 550 mg, or about 2.76 g of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[326] In some embodiments, the bacterial composition comprises about 2xlO¹⁰, 2.1xlO¹⁰, 2.2xlO¹⁰, 2.3xlO¹⁰, 2.4xlO¹⁰, 2.5xlO¹⁰, 2.6xlO¹⁰, 2.7xlO¹⁰, 2.8xlO¹⁰, 2.9xlO¹⁰, 3xl0¹⁰, 3.1xl0¹⁰, 3.2xlO¹⁰, 3.3xl0¹⁰, 3.4xlO¹⁰, 3.5xl0¹⁰, 3.6xlO¹⁰, 3.7xlO¹⁰, 3.8xl0¹⁰, 3.9xlO¹⁰, 4xlO¹⁰, 5xlO¹⁰, 6xlO¹⁰, 7xlO¹⁰, 8xlO¹⁰, 9xlO¹⁰, IxlO¹¹, l. lxlO¹¹, 1.2xlOⁿ, 1.3xlOⁿ, 1.4xlOⁿ, 1.5xlOⁿ, 1.6xlOⁿ, 1.7xlOⁿ, 1.8xlOⁿ, 1.9xlOⁿ, 2xlO^u, 2.1xlOⁿ, 2.2xlOⁿ, 2.3xlOⁿ, 2.4xlO^u, 2.5xlO^u, 2.6xlO^u, 2.7xlO^u, 2.8xlOⁿ, 2.9xlO^u, 3xlOⁿ, 3. IxlO¹¹, 3.2xlOⁿ, 3.3xlO^u, 3.4xlO^u, 3.5xlO^u, 3.6xlO^u, 3.7xlOⁿ, 3.8xlO^u, 3.9xlO^u, 4xlOⁿ 5xlO^u, 6xlO^u, 7xlO^u, 8xlO^u, 9xlO^u, IxlO¹², 1.5xl0¹² total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 8xlO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 1.6xlOⁿ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 3.2xlO^u total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 6.4xlO^u total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 8xl0ⁿ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 9.6xlO^u total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 12.8xlOⁿ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 16xlOⁿ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 1.6 x 10¹⁰ to about 1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 1.6 x 10¹⁰ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 8 x 10¹⁰ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 8 x 10¹⁰ to about 1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 3.2 x 10¹⁰ to about 9.6 x 10¹⁰ cells total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 4.8 x 10¹⁰ to about 9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 6.4 x 10¹⁰ to about 9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 9.6 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 9.6 x 10¹¹ to about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. In some embodiments, the bacterial composition comprises about 12.8 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. Herein, total cells is determined by total cell count (e.g., determined by Coulter counter).

[327] In some embodiments, the bacterial composition comprises about 1.6 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[328] In some embodiments, the bacterial composition comprises about 8 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[329] In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[330] In some embodiments, the bacterial composition comprises about 3.2 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[331] In some embodiments, the bacterial composition comprises about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[332] In some embodiments, the bacterial composition comprises about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[333] In some embodiments, the bacterial composition comprises about 1.6 x 10¹⁰ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[334] In some embodiments, the bacterial composition comprises about 1.6 x 10¹⁰ to about

1.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[335] In some embodiments, the bacterial composition comprises about 1.6 x 10¹¹ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[336] In some embodiments, the bacterial composition comprises about 8 x 10¹⁰ to about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[337] In some embodiments, the bacterial composition comprises about 3.2 x 10¹⁰ to about

9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[338] In some embodiments, the bacterial composition comprises about 4.8 x 10¹⁰ to about

9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329. [339] In some embodiments, the bacterial composition comprises about 6.4 x IO¹⁰ to about 9.6 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[340] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x

10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[341] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 1.6 x

10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[342] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[343] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[344] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[345] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[346] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[347] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[348] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[349] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ to about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B

50329. [350] In some embodiments, the bacterial composition, e.g., bacterial composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[351] In some embodiments, the bacterial composition comprising Pre votella bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., mini-tablets comprised in a capsule). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[352] In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 solid dosage forms are administered, e.g., once or twice daily to a subject.

[353] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x IO¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹⁰total cells.

[354] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 8 x IO¹⁰ total cells.

[355] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 1.6 x 10¹¹ total cells.

[356] In some embodiments, 1 solid dosage form (e.g., tablet or capsule) is administered (e.g., is for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 2 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form (e.g., each solid dose form) comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 3 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 4 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 5 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10ⁿtotal cells. In some embodiments, 6 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 8 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. In some embodiments, 10 solid dosage forms (e.g., tablets or capsules) are administered (e.g., are for administration) e.g., once or twice daily to a subject, wherein the solid dosage form comprises a dose of bacteria of about 3.2 x 10¹¹ total cells. For clarity, about 3.2 x 10¹¹ total cells includes total cell counts within ±5% of 3.2 x 10¹¹ total cells e.g., 3.35 x 10¹¹ total cells.

[357] In some embodiments, the bacterial composition is prepared as a solid dosage form. In some embodiments, provided herein are solid dosage forms comprising the Prevotella histicola bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, each tablet comprises about 8 x IO¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each tablet comprises about 3.2 x 10¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, each capsule comprises about 8 x IO¹⁰ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella histicola bacteria. In some embodiments, each capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella histicola bacteria.

[358] In some embodiments, the bacterial composition, e.g., pharmaceutical composition is a powder. The powder can be resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage or a food), e.g., for administration to a subject.

[359] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x IO¹⁰ total cells are administered (e.g., are for administration) per day.

[360] In some embodiments, a dose of Prevotella histicola bacteria of about 1.6 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[361] In some embodiments, a dose of Prevotella histicola bacteria of about 3.2 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[362] In some embodiments, a dose of Prevotella histicola bacteria of about 6.4 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[363] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x 10¹¹ total cells are administered (e.g., are for administration) per day. [364] In some embodiments, a dose of Prevotella histicola bacteria of about 9.6 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[365] In some embodiments, a dose of Prevotella histicola bacteria of about 12.8 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[366] In some embodiments, a dose of Prevotella histicola bacteria of about 16 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[367] In some embodiments, the solid dosage form is a tablet. In some embodiments, the tablet is an enteric coated tablet. In some embodiments, the enteric coated tablet is from 5mm to 18mm in diameter (size refers to size prior to application of enteric coat). In some embodiments, the tablet comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the tablet comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the tablet are lyophilized.

[368] In some embodiments, the solid dosage form is a capsule. In some embodiments, the capsule is an enteric coated capsule. In some embodiments, the enteric coated capsule is a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule. In some embodiments, the capsule comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, the Prevotella bacteria in the capsule are lyophilized. In some embodiments, the capsule comprises gelatin. In some embodiments, the capsule comprises HPMC.

[369] In some embodiments, provided herein are solid dosage forms comprising the Prevotella bacteria. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule. In some embodiments, the enteric coating comprises a polymethacrylate- based copolymer. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1). In some embodiments, the enteric coating comprises methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P or Eudragit L30-D55).

[370] In some embodiments, each tablet comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 8 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[371] In some embodiments, each tablet comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 1.6 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[372] In some embodiments, each tablet comprises about 3.2 x 10ⁿtotal cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 tablets are administered, e.g., once or twice daily to a subject. In some embodiments, 1 tablet (e.g., comprising about 3.2 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 tablets (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[373] In some embodiments, each capsule comprises about 1.6 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[374] In some embodiments, each capsule comprises about 8 x IO¹⁰ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 8 x IO¹⁰ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. . In some embodiments, 5 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 8 x IO¹⁰ total cells) are administered, e.g., once or twice daily to a subject.

[375] In some embodiments, each capsule comprises about 1.6 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 1.6 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 1.6 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[376] In some embodiments, each capsule comprises about 3.2 x 10¹¹ total cells of the Prevotella bacteria. In some embodiments, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 capsules are administered, e.g., once or twice daily to a subject. In some embodiments, 1 capsule (e.g., comprising about 3.2 x 10¹¹ total cells) is administered, e.g., once or twice daily to a subject. In some embodiments, 2 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 3 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 4 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 5 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 6 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 8 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject. In some embodiments, 10 capsules (e.g., each comprising about 3.2 x 10¹¹ total cells) are administered, e.g., once or twice daily to a subject.

[377] In some embodiments, the Prevotella bacteria in the capsule are lyophilized (e.g., in a powder). In some embodiments, the Prevotella bacteria in the capsule are lyophilized in a powder, and the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide.

[378] In some embodiments, at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% of the bacteria in the composition are of the Prevotella strain. In some embodiments, at least 99% of the bacteria in the composition are of the Prevotella strain. In some embodiments, the bacteria in the composition are essentially (e.g., about 100%) of the Prevotella strain.

[379] In some embodiments, about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%,

11%, 12%, 13%, 14%, 15%, 16%, 17%, 18%, 19%, 20%, 21%, 22%, 23%, 24%, 25%,

26%, 27%, 28%, 29%, 30%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%,

41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%,

56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%,

71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%,

86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% of the protein in the pharmaceutical composition is Prevotella strain bacteria protein.

[380] In some embodiments, the Prevotella bacteria may be quantified based on total cells, e.g., total cell count (TCC) (e.g., determined by Coulter counter).

[381] In some embodiments, the bacterial composition is administered orally. In some embodiments, the administration to the subject once daily. In some embodiments, the bacterial composition is administered in 2 or more doses (e.g., 3 or more, 4 or more or 5 or more doses). In some embodiments, the administration to the subject of the two or more doses are separated by at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days or 21 days.

[382] In some embodiments, the bacterial composition is administered once daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[383] In some embodiments, the bacterial composition is administered twice daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[384] In some embodiments, the bacterial composition is formulated as a tablet. In some embodiments, the bacterial composition is formulated as a capsule. In some embodiments, the bacterial formulation (e.g., composition) comprises an enteric coating or micro encapsulation. In some embodiments, the enteric coating allows release of the bacterial composition in the small intestine, e.g., in the upper small intestine, e.g., in the duodenum.

[385] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal (e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee).

[386] In some embodiments, the bacterial composition comprises an enteric coating or micro encapsulation. In some embodiments, the enteric coating or micro encapsulation improves targeting to a desired region of the gastrointestinal tract. For example, in some embodiments, the bacterial composition comprises an enteric coating and/or microcapsules that dissolves at a pH associated with a particular region of the gastrointestinal tract. In some embodiments, the enteric coating and/or microcapsules dissolve at a pH of about 5.5 - 6.2 to release in the duodenum, at a pH value of about 7.2 - 7.5 to release in the ileum, and/or at a pH value of about 5.6 - 6.2 to release in the colon. Exemplary enteric coatings and microcapsules are described, for example, in U.S. Pat. Pub. No. 2016/0022592, which is hereby incorporated by reference in its entirety.

[387] In some aspects, provided are bacterial compositions for administration to subjects. In some embodiments, the bacterial compositions are combined with additional active and/or inactive materials in order to produce a final product, which may be in single dosage unit or in a multi-dose format. In some embodiments, the bacterial compositions are combined with an adjuvant such as an immuno-adjuvant (e.g., STING agonists, TLR agonists, NOD agonists).

[388] In some embodiments, the bacterial composition comprises at least one carbohydrate. A “carbohydrate” refers to a sugar or polymer of sugars. The terms “saccharide,” “polysaccharide,” “carbohydrate,” and “oligosaccharide” may be used interchangeably. Most carbohydrates are aldehydes or ketones with many hydroxyl groups, usually one on each carbon atom of the molecule. Carbohydrates generally have the molecular formula CnEknOn. A carbohydrate may be a monosaccharide, a disaccharide, tri saccharide, oligosaccharide, or polysaccharide. The most basic carbohydrate is a monosaccharide, such as glucose, sucrose, galactose, mannose, ribose, arabinose, xylose, and fructose. Disaccharides are two joined monosaccharides. Exemplary disaccharides include sucrose, maltose, cellobiose, and lactose. Typically, an oligosaccharide includes between three and six monosaccharide units (e.g., raffinose, stachyose), and polysaccharides include six or more monosaccharide units. Exemplary polysaccharides include starch, glycogen, and cellulose. Carbohydrates may contain modified saccharide units such as 2’ -deoxyribose wherein a hydroxyl group is removed, 2’-fluororibose wherein a hydroxyl group is replaced with a fluorine, or N-acetylglucosamine, a nitrogen-containing form of glucose (e.g., 2’ -fluororibose, deoxyribose, and hexose). Carbohydrates may exist in many different forms, for example, conformers, cyclic forms, acyclic forms, stereoisomers, tautomers, anomers, and isomers.

[389] In some embodiments, the bacterial composition comprises at least one lipid. As used herein a “lipid” includes fats, oils, triglycerides, cholesterol, phospholipids, fatty acids in any form including free fatty acids. Fats, oils and fatty acids can be saturated, unsaturated (cis or trans) or partially unsaturated (cis or trans). In some embodiments the lipid comprises at least one fatty acid selected from lauric acid (12:0), myristic acid (14:0), palmitic acid (16:0), palmitoleic acid (16: 1), margaric acid (17:0), heptadecenoic acid (17: 1), stearic acid (18:0), oleic acid (18: 1), linoleic acid (18:2), linolenic acid (18:3), octadecatetraenoic acid (18:4), arachidic acid (20:0), eicosenoic acid (20:1), eicosadienoic acid (20:2), eicosatetraenoic acid (20:4), eicosapentaenoic acid (20:5) (EP A), docosanoic acid (22:0), docosenoic acid (22: 1), docosapentaenoic acid (22:5), docosahexaenoic acid (22:6) (DHA), and tetracosanoic acid (24:0). In some embodiments the composition comprises at least one modified lipid, for example a lipid that has been modified by cooking. [390] In some embodiments, the bacterial composition comprises at least one supplemental mineral or mineral source. Examples of minerals include, without limitation: chloride, sodium, calcium, iron, chromium, copper, iodine, zinc, magnesium, manganese, molybdenum, phosphorus, potassium, and selenium. Suitable forms of any of the foregoing minerals include soluble mineral salts, slightly soluble mineral salts, insoluble mineral salts, chelated minerals, mineral complexes, non-reactive minerals such as carbonyl minerals, and reduced minerals, and combinations thereof.

[391] In some embodiments, the bacterial composition comprises at least one supplemental vitamin. The at least one vitamin can be fat-soluble or water-soluble vitamins. Suitable vitamins include but are not limited to vitamin C, vitamin A, vitamin E, vitamin B12, vitamin K, riboflavin, niacin, vitamin D, vitamin B6, folic acid, pyridoxine, thiamine, pantothenic acid, and biotin. Suitable forms of any of the foregoing are salts of the vitamin, derivatives of the vitamin, compounds having the same or similar activity of the vitamin, and metabolites of the vitamin.

[392] In some embodiments, the bacterial composition comprises an excipient. Nonlimiting examples of suitable excipients include a buffering agent, a preservative, a stabilizer, a binder, a compaction agent, a lubricant, a dispersion enhancer, a disintegration agent, a flavoring agent, a sweetener, and a coloring agent.

[393] In some embodiments, the excipient is a buffering agent. Non-limiting examples of suitable buffering agents include sodium citrate, magnesium carbonate, magnesium bicarbonate, calcium carbonate, and calcium bicarbonate.

[394] In some embodiments, the excipient comprises a preservative. Non-limiting examples of suitable preservatives include antioxidants, such as alpha-tocopherol and ascorbate, and antimicrobials, such as parabens, chlorobutanol, and phenol.

[395] In some embodiments, the bacterial composition comprises a binder as an excipient. Non-limiting examples of suitable binders include starches, pregelatinized starches, gelatin, polyvinylpyrolidone, cellulose, methylcellulose, sodium carboxymethylcellulose, ethylcellulose, polyacrylamides, polyvinyloxoazolidone, polyvinylalcohols, C12-C18 fatty acid alcohol, polyethylene glycol, polyols, saccharides, oligosaccharides, and combinations thereof.

[396] In some embodiments the composition comprises a lubricant as an excipient. Nonlimiting examples of suitable lubricants include magnesium stearate, calcium stearate, zinc stearate, hydrogenated vegetable oils, sterotex, polyoxyethylene monostearate, talc, polyethyleneglycol, sodium benzoate, sodium lauryl sulfate, magnesium lauryl sulfate, and light mineral oil.

[397] In some embodiments, the bacterial composition comprises a dispersion enhancer as an excipient. Non-limiting examples of suitable dispersants include starch, alginic acid, polyvinylpyrrolidones, guar gum, kaolin, bentonite, purified wood cellulose, sodium starch glycolate, isoamorphous silicate, and microcrystalline cellulose as high HLB emulsifier surfactants.

[398] In some embodiments, the bacterial composition comprises a disintegrant as an excipient. In some embodiments the disintegrant is a non-effervescent disintegrant. Nonlimiting examples of suitable non-effervescent disintegrants include starches such as com starch, potato starch, pregelatinized and modified starches thereof, sweeteners, clays, such as bentonite, micro-crystalline cellulose, alginates, sodium starch glycolate, gums such as agar, guar, locust bean, karaya, pectin, and tragacanth. In some embodiments, the disintegrant is an effervescent disintegrant. Non-limiting examples of suitable effervescent disintegrants include sodium bicarbonate in combination with citric acid, and sodium bicarbonate in combination with tartaric acid.

[399] In some embodiments, the composition (e.g., bacterial composition) is a food product (e.g., a food or beverage) such as a health food or beverage, a food or beverage for infants, a food or beverage for pregnant women, athletes, senior citizens or other specified group, a functional food, a beverage, a food or beverage for specified health use, a dietary supplement, a food or beverage for patients, or an animal feed. Specific examples of the foods and beverages include various beverages such as juices, refreshing beverages, tea beverages, drink preparations, jelly beverages, and functional beverages; alcoholic beverages such as beers; carbohydrate-containing foods such as rice food products, noodles, breads, and pastas; paste products such as fish hams, sausages, paste products of seafood; retort pouch products such as curries, food dressed with a thick starchy sauces, and Chinese soups; soups; dairy products such as milk, dairy beverages, ice creams, cheeses, and yogurts; fermented products such as fermented soybean pastes, yogurts, fermented beverages, and pickles; bean products; various confectionery products, including biscuits, cookies, and the like, candies, chewing gums, gummies, cold desserts including jellies, cream caramels, and frozen desserts; instant foods such as instant soups and instant soybean soups; microwavable foods; and the like. Further, the examples also include health foods and beverages prepared in the forms of powders, granules, tablets, capsules, liquids, pastes, and jellies.

[400] In some embodiments the composition (e.g., bacterial composition) is a food product for animals, including humans. The animals, other than humans, are not particularly limited, and the composition can be used for various livestock, poultry, pets, experimental animals, and the like. Specific examples of the animals include pigs, cattle, horses, sheep, goats, chickens, wild ducks, ostriches, domestic ducks, dogs, cats, rabbits, hamsters, mice, rats, monkeys, and the like, but the animals are not limited thereto.

Dose Forms

[401] Dose forms comprising Prevotella histicola bacteria are also provided herein, e.g., for use in methods to treat or prevent inflammation (such as inflammation associated with psoriasis or atopic dermatitis or psoriatic arthritis) in a subject (e.g., a human subject). A bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola bacteria can be formulated as a solid dose form, e.g., for oral administration. In some embodiments, the bacterial composition (e.g., pharmaceutical composition) comprising Prevotella histicola bacteria is prepared as a powder (e.g., for resuspension or for use in a solid dose form (such as a capsule)) or as a solid dose form, such as a tablet, a mini-tablet, a capsule, or a powder; or a combination of these forms (e.g., mini -tablets comprised in a capsule)). The powder can comprise lyophilized bacteria. In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the powder further comprises mannitol. In some embodiments, the powder further comprises magnesium stearate. In some embodiments, the powder further comprises colloidal silicon dioxide. In some embodiments, the Prevotella histicola bacteria are gamma irradiated.

[402] The solid dose form (also referred to as solid dosage form herein) can comprise one or more excipients, e.g., pharmaceutically acceptable excipients. The Prevotella histicola bacteria in the solid dose form can be isolated Prevotella histicola bacteria. Optionally, the Prevotella histicola bacteria in the solid dose form can be lyophilized. Optionally, the Prevotella histicola bacteria in the solid dose form are live. Optionally, the Prevotella histicola bacteria in the solid dose form are non-live. Optionally, the Prevotella histicola bacteria in the solid dose form are gamma irradiated. The solid dose form can comprise a tablet. The solid dose form can comprise a capsule. The solid dose form can comprise a tablet, a mini -tablet, a capsule, or a powder; or a combination of these forms e.g., minitablets comprised in a capsule).

[403] The Prevotella histicola bacteria in the solid dose form can be in a powder (e.g., the powder comprises lyophilized Prevotella histicola bacteria). In some embodiments, the powder further comprises mannitol, magnesium stearate, and/or colloidal silicon dioxide. In some embodiments, the powder further comprises mannitol, magnesium stearate, and colloidal silicon dioxide. Optionally, the Prevotella histicola bacteria in the powder can be lyophilized. Optionally, the Prevotella histicola bacteria in the powder are live. Optionally, the Prevotella histicola bacteria in the solid dose form are non-live. Optionally, the Prevotella histicola bacteria in the powder are gamma irradiated.

[404] In some embodiments, the lyophilized Prevotella histicola bacteria (e.g., powder) is resuspended (e.g., in a liquid such as a solution, buffer, water or other beverage or a food), e.g., for administration to a subject.

[405] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) provided herein is prepared as a solid dosage form comprising Prevotella histicola bacteria and a pharmaceutically acceptable carrier.

[406] In some embodiments, the bacterial composition (e.g., pharmaceutical composition) provided herein is prepared as a solid dosage form comprising Prevotella histicola bacteria and a pharmaceutically acceptable carrier. The solid dosage form can comprise a tablet, a mini-tablet, a capsule, a pill, or a powder; or a combination of these forms (e.g., minitablets comprised in a capsule).

[407] In some embodiments, the solid dosage form comprises a capsule. The capsule can comprise an enteric coating. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. In some embodiments, the capsule is a size 0 capsule.

[408] In some embodiments, the solid dosage form comprises a tablet (> 4mm) (e.g., 5mm-18mm). For example, the tablet is a 5mm, 6mm, 7mm, 8mm, 9mm, 10mm, 11mm, 12mm, 13mm, 14mm, 15mm, 16mm, 17mm or 18mm tablet. In some embodiments, the tablet is a 17mm tablet. The size refers to the diameter of the tablet, as is known in the art.

[409] In some embodiments, the solid dosage form comprises a mini-tablet. The mini-tablet can be in the size range of lmm-4 mm range. E.g., the mini-tablet can be a 1mm mini-tablet, 1.5 mm mini-tablet, 2mm mini-tablet, 3mm mini-tablet, or 4mm mini-tablet. The size refers to the diameter of the mini-tablet, as is known in the art. As used herein, the size of the mini-tablet refers to the size of the mini-tablet prior to application of an enteric coating.

[410] As used herein, the size of the tablet refers to the size of the tablet, mini-tablet or capsule prior to application of an enteric coating.

[411] The mini-tablets can be in a capsule. The capsule can be a size 00, size 0, size 1, size 2, size 3, size 4, or size 5 capsule. The capsule that contains the mini -tablets can comprise a single layer coating, e.g., a non-enteric coating such as gelatin or HPMC. The mini -tablets can be inside a capsule: the number of mini-tablets inside a capsule will depend on the size of the capsule and the size of the mini-tablets. As an example, a size 0 capsule can contain 31-35 (an average of 33) mini-tablets that are 3mm mini-tablets.

Coating

[412] The solid dosage form (e.g., capsule, tablet or minitablet) described herein can be enterically coated, e.g., with one enteric coating layer or with two layers of enteric coating, e.g., an inner enteric coating and an outer enteric coating. The inner enteric coating and outer enteric coating are not identical (e.g., the inner enteric coating and outer enteric coating do not contain the same components in the same amounts). The enteric coating allows for release of the Prevotella histicola bacteria, e.g., in the small intestine, e.g., in the upper small intestine.

[413] Release of the Prevotella histicola bacteria in the small intestine allows the bacteria contained therein to target and affect cells (e.g., epithelial cells and/or immune cells) located at these specific locations, e.g., which can cause a local effect in the gastrointestinal tract and/or cause a systemic effect (e.g., an effect outside of the gastrointestinal tract).

[414] EUDRAGIT is the brand name for a diverse range of polymethacrylate- based copolymers that can be used an enteric coatings. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives.

[415] Examples of other materials that can be used in the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) include cellulose acetate phthalate (CAP), cellulose acetate trimellitate (CAT), poly(vinyl acetate phthalate) (PVAP), hydroxypropyl methylcellulose phthalate (HPMCP), fatty acids, waxes, shellac (esters of aleurtic acid), plastics, plant fibers, zein, Aqua-Zein® (an aqueous zein formulation containing no alcohol), amylose starch, starch derivatives, dextrins, methyl acrylate-methacrylic acid copolymers, cellulose acetate succinate, hydroxypropyl methyl cellulose acetate succinate (hypromellose acetate succinate), methyl methacrylatemethacrylic acid copolymers, and/or sodium alginate.

[416] The enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) can include a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1).

[417] The one enteric coating can include methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) (such as Kollicoat MAE 100P).

[418] The one enteric coating can include a Eudragit copolymer, e.g., a Eudragit L (e.g., Eudragit L 100-55; Eudragit L 30 D-55), a Eudragit S, a Eudragit RL, a Eudragit RS, a Eudragit E, or a Eudragit FS (e.g., Eudragit FS 30 D).

[419] Other examples of materials that can be used in the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) include those described in, Hussan et al., IOSR Journal of Pharmacy volume 2, pages 5-11 (Nov- Dec 2012) and Hua, Frontiers in Pharmacology volume 11, article 524 (Apr 2020).

[420] Other examples of materials that can be used in the enteric coating (e.g., the one enteric coating or the inner enteric coating and/or the outer enteric coating) include those described in, e.g., U.S. 6312728; U.S. 6623759; U.S. 4775536; U.S. 5047258; U.S. 5292522; U.S. 6555124; U.S. 6638534; U.S. 2006/0210631; U.S. 2008/200482; U.S. 2005/0271778; U.S. 2004/0028737; WO 2005/044240.

[421] See also, e.g., U.S. 9233074, which provides pH dependent, enteric polymers that can be used with the solid dosage forms provided herein, including methacrylic acid copolymers, polyvinylacetate phthalate, hydroxypropylmethyl cellulose acetate succinate, hydroxypropylmethyl cellulose phthalate and cellulose acetate phthalate; suitable methacrylic acid copolymers include: poly(methacrylic acid, methyl methacrylate) 1 : 1 sold, for example, under the Eudragit LI 00 trade name; poly(methacrylic acid, ethyl acrylate) 1 : 1 sold, for example, under the Eudragit LI 00-55 trade name; partially- neutralized poly(methacrylic acid, ethyl acrylate) 1 : 1 sold, for example, under the Kollicoat MAE- 100P trade name; and poly(methacrylic acid, methyl methacrylate) 1 :2 sold, for example, under the Eudragit SI 00 trade name.

[422] In some embodiments, the solid dosage form comprises a sub-coat, e.g., under the enteric coating (e.g., one enteric coating). The sub-coat can be used, e.g., to visually mask the appearance of the Prevotella histicola bacteria and/or components (e.g., excipients) therein.

[423] The coating level (also referred to herein as thickness) of the enteric coating on a solid dosage form influences the site of release of the Prevotella histicola bacteria from the solid dosage form after oral administration.

[424] In some embodiments, the enteric coating is at a coating level of between about 5 to about 31 mg per solid dose form (e.g., per capsule (e.g., size 0 capsule) or per tablet (e.g., 17 mm tablet)) (e.g., or an equivalent coating level for the given sized solid dose form). For example, if a size 0 capsule has a coating level of between about 5 to about 31 mg per capsule, a smaller capsule will have a coating level that is proportionate to about 5 to about 31 mg for its size.

[425] In some embodiments, the enteric coating is at a coating level of about 5 mg; about 9 mg; about 14 mg; about 19 mg; about 25 mg; or about 31 mg per solid dose form (e.g., per capsule (e.g., size 0 capsule) or per tablet (e.g., 17 mm tablet)) (e.g., or an equivalent coating level for the given sized solid dose form). For example, if a size 0 capsule has a coating level of about 5 mg, a smaller capsule will have a coating level that is proportionate to about 5 mg for its size.

[426] In some embodiments, the enteric coating is at a coating level of between about 1 mg/cm² to about 6 mg/cm² per solid dose form (e.g., per capsule (e.g., between about 5 mg to about 31 mg per size 0 capsule)). In some embodiments, the enteric coating is at a coating level of about 1 mg/cm² (e.g., about 5 mg per size 0 capsule); about 1.7 mg/cm² (e.g., about 9 mg per size 0 capsule); about 2.7 mg/cm² (e.g., about 14 mg per size 0 capsule); about 3.7 mg/cm² (e.g., about 19 mg per size 0 capsule); about 4.8 mg/cm² (e.g., about 25 mg per size 0 capsule); or about 6 mg/cm² (e.g., about 31 mg per size 0 capsule) per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 1 mg/cm² per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 1.7 mg/cm² per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 2.7 mg/cm² per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 3.7 mg/cm² per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 4.8 mg/cm² per solid dose form (such as a capsule). In some embodiments, the enteric coating is at a coating level of about 6 mg/cm² per solid dose form (such as a capsule). [427] In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 :1). In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) such as Eudragit L copolymer, such as Eudragit L 30 D-55. In some embodiments, the enteric coating comprises a methacrylic acid ethyl acrylate (MAE) copolymer (1 : 1) such as such as Kollicoat MAE 100P.

[428] In some embodiments, the enteric coating comprises a combination of two copolymers (e.g., a first copolymer and a second copolymer). In some embodiments, the combination of two copolymers comprises a combination of a methacrylic acid-ethyl acrylate copolymer (1 : 1) and a poly(methyl acrylate-co-methyl methacrylate-co- methacrylic acid) copolymer. In some embodiments, the combination of two copolymers comprises a combination of a Eudragit L copolymer and a Eudragit FS copolymer. In some embodiments, the combination of two copolymers comprises a combination of a methacrylic acid-ethyl acrylate copolymer (1 : 1) (such as Eudragit L copolymer, such as Eudragit L 30 D-55), and a poly(methyl acrylate-co-methyl methacrylate-co-methacrylic acid) copolymer (such as Eudragit FS copolymer, such as Eudragit FS 30 D). In some embodiments, the ratio of the first copolymer to the second copolymer is between about 100%:0% to about 0%: 100%. In some embodiments, the ratio of the first copolymer to the second copolymer is between about 75%:25% to about 25%:75%. In some embodiments, the ratio of the first copolymer to the second copolymer is about 100%:0; about 75%:25%; about 50%:50%; about 25%:75%; about 17.5%:82.5%; or about 0: 100%. In some embodiments, the first copolymer comprises a Eudragit L copolymer, such as Eudragit L 30 D-55 and the second copolymer comprises a Eudragit FS copolymer, such as Eudragit FS 30 D.

[429] The solid dose form can comprise a coating. The solid dose form can comprise a single layer coating, e.g., enteric coating, e.g., a Eudragit-based coating, e.g., EUDRAGIT L30 D-55, tri ethyl citrate, and talc. The solid dose form can comprise two layers of coating. For example, an inner coating can comprise, e.g., EUDRAGIT L30 D-55, triethylcitrate, talc, citric acid anhydrous, and sodium hydroxide, and an outer coating can comprise, e.g., EUDRAGIT L30 D-55, triethylcitrate, and talc. EUDRAGIT is the brand name for a diverse range of polymethacrylate-based copolymers. It includes anionic, cationic, and neutral copolymers based on methacrylic acid and methacrylic/acrylic esters or their derivatives. Eudragits are amorphous polymers having glass transition temperatures between 9 to > 150°C. Eudragits are non-biodegradable, nonabsorbable, and nontoxic. Anionic Eudragit L dissolves at pH > 6 and is used for enteric coating, while Eudragit S, soluble at pH > 7 is used for colon targeting. Eudragit RL and RS, having quaternary ammonium groups, are water insoluble, but swellable/permeable polymers which are suitable for the sustained release film coating applications. Cationic Eudragit E, insoluble at pH > 5, can prevent drug release in saliva.

Dosage

[430] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[431] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about

[432] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[433] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[434] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[435] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about

9.6 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[436] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[437] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[438] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x IO¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[439] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 9.6 x 10¹¹ to about 12.8 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[440] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about

12.8 x 10¹¹ to about 16 x 10¹¹ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[441] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 3.2 x IO¹⁰ to about 9.6 x IO¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[442] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about

4.8 x 10¹⁰ to about 9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[443] In some embodiments, the bacterial composition, e.g., pharmaceutical composition (e.g., composition of the total dose administered, e.g., once or twice daily) comprises about 6.4 x 10¹⁰ to about 9.6 x 10¹⁰ total cells of Prevotella histicola, e.g., of Prevotella Strain B 50329.

[444] In some embodiments, the dose of bacterial composition is administered as solid dosage form(s) comprising the Prevotella histicola bacteria. In some embodiments, the solid dosage form comprises an enteric coating. In some embodiments, the solid dosage form is a tablet, e.g., an enteric coated tablet. In some embodiments, the solid dosage form is a mini-tablet, e.g., an enteric coated mini-tablet. In some embodiments, the solid dosage form is a capsule, e.g., an enteric coated capsule.

[445] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x 10¹⁰ total cells are administered (e.g., are for administration) per day.

[446] In some embodiments, a dose of Prevotella histicola bacteria of about 1.6 x 10¹¹ total cells are administered (e.g., are for administration) per day. [447] In some embodiments, a dose of Prevotella histicola bacteria of about 3.2 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[448] In some embodiments, a dose of Prevotella histicola bacteria of about 6.4 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[449] In some embodiments, a dose of Prevotella histicola bacteria of about 8 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[450] In some embodiments, a dose of Prevotella histicola bacteria of about 9.6 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[451] In some embodiments, a dose of Prevotella histicola bacteria of about 12.8 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[452] In some embodiments, a dose of Prevotella histicola bacteria of about 16 x 10¹¹ total cells are administered (e.g., are for administration) per day.

[453] In some embodiments, the Prevotella histicola bacteria are quantified based on total cells, e.g., total cell count (TCC) (e.g., determined by Coulter counter).

Gamma-irradiation

[454] Powders (e.g., of Prevotella histicola bacteria) can be gamma-irradiated at 17.5 kGy radiation unit at ambient temperature.

[455] Frozen biomasses (e.g., of Prevotella histicola bacteria) can be gamma-irradiated at 25 kGy radiation unit in the presence of dry ice.

Methods of Use

[456] Bacterial compositions (e.g., prepared as solid dosage forms) described herein allow, e.g., for oral administration of bacteriacontained therein.

[457] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of inflammation, autoimmunity, a metabolic condition, or a dysbiosis.

[458] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection).

[459] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of an inflammatory disease. [460] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of psoriasis.

[461] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of atopic dermatitis.

[462] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of psoriatic arthritis.

[463] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of an autoimmune disease.

[464] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of a metabolic disease.

[465] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of a dysbiosis.

[466] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used to decrease inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels).

[467] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used to decrease IgE levels.

[468] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of cytokine storm (cytokine release syndrome) in a subject in need thereof. In some embodiments, the cytokine storm is due to elevation in IL-8, IL-6, IL-ip, and/or TNFa expression levels.

[469] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of bacterial septic shock.

[470] In some embodiments, bacterial compositions (e.g., prepared as solid dosage forms) described herein can be used in the treatment and/or prevention of a viral infection.

[471] Methods of using a bacterial composition (e.g., prepared as a solid dosage form) (e.g., for oral administration) (e.g., for pharmaceutical use) comprising bacteria (e.g., a therapeutically effective amount thereof), wherein the bacteria comprises Prevotella histicola bacteria, and wherein the bacterial composition (e.g., prepared as a solid dosage form) further comprises the disclosed components are described herein.

[472] The methods and administered bacterial compositions (e.g., prepared as solid dosage forms) described herein allow, e.g., for oral administration of bacteria contained therein (e.g., a therapeutically effective amount thereof). The bacterial composition (e.g., prepared as a solid dosage form) can be administered to a subject is a fed or fasting state. The bacterial composition (e.g., prepared as a solid dosage form) can be administered, e.g., on an empty stomach (e.g., one hour before eating or two hours after eating). The bacterial composition (e.g., prepared as a solid dosage form) can be administered one hour before eating. The bacterial composition (e.g., prepared as a solid dosage form) an be administered two hours after eating. The bacterial composition (e.g., prepared as a solid dosage form) can be administered one hour before drinking (e.g., drinking an acidic drink). The bacterial composition (e.g., prepared as a solid dosage form) can be administered one hour after drinking (e.g., drinking an acidic drink).

[473] A bacterial composition (e.g., prepared as a solid dosage form) for use in the treatment and/or prevention of inflammation, autoimmunity, a metabolic condition, or a dysbiosis is provided herein.

[474] A bacterial composition (e.g., prepared as a solid dosage form) for use in the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection) is provided herein.

[475] A bacterial composition (e.g., prepared as a solid dosage form) for use in decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels) is provided herein.

[476] A bacterial composition (e.g., prepared as a solid dosage form) for use in decreasing inflammatory cytokine expression is provided herein. In some embodiments, the pro- inflammatory cytokine is IL-31, IL-23p40, IL-17, and/or IL-13. In some embodiments, the pro-inflammatory cytokine is IL-4, IL-5, and/or IL-13.

[477] A bacterial composition (e.g., prepared as a solid dosage form) for use in decreasing IgE levels is provided herein.

[478] Use of a bacterial composition (e.g., prepared as a solid dosage form) for the preparation of a medicament for the treatment and/or prevention of inflammation, autoimmunity, a metabolic condition, or a dysbiosis is provided herein.

[479] Use of a bacterial composition (e.g., prepared as a solid dosage form) for the preparation of a medicament for the treatment and/or prevention of bacterial septic shock, cytokine storm and/or viral infection (such as a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection) is provided herein. [480] Use of a bacterial composition (e.g., prepared as a solid dosage form) for the preparation of a medicament for decreasing inflammatory cytokine expression (e.g., decreased IL-8, IL-6, IL-ip, and/or TNFa expression levels) is provided herein.

[481] Use of a bacterial composition (e.g., prepared as a solid dosage form) for the preparation of a medicament for decreasing inflammatory cytokine expression is provided herein. In some embodiments, the pro-inflammatory cytokine is IL-31, IL-23p40, IL-17, and/or IL-13. In some embodiments, the pro-inflammatory cytokine is IL-4, IL-5, and/or IL-13.

[482] Use of a bacterial composition (e.g., prepared as a solid dosage form) for the preparation of a medicament for decreasing IgE levels is provided herein.

Additional Therapeutic

[483] In some aspects, the methods provided herein include the administration to a subject of a bacterial composition described herein either alone or in combination with an additional therapeutic. In some embodiments, the additional therapeutic is an immunosuppressant, or a steroid. In some embodiments, the additional therapeutic is a topical treatment. In some embodiments, the topical treatment comprises a topical corticosteroid (TCS), a topical calcineurin inhibitor (TCI) (Katoh, 2019), a topical Janus Kinase (JAK) or Phosphodiesterase 4 (PDE) inhibitor (Bieber, 2021).

[484] In some aspects, the methods provided herein include use of an emollient cream, gel or ointment. In some embodiments, a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel or ointment is used. In some embodiments, the emollient cream, gel or ointment is used daily (e.g., twice daily) (or more, as needed) for at least 14 consecutive days immediately prior use of the Prevotella histicola bacteria. In some embodiments, the emollient cream, gel or ointment is used daily (e.g., twice daily) (or more, as needed) while the Prevotella histicola bacteria are used. In some embodiments, the emollient cream, gel or ointment is used daily (e.g., twice daily) (or more, as needed) for at least 14 consecutive days immediately prior use of the Prevotella histicola bacteria and is used daily (e.g., twice daily) (or more, as needed) while the Prevotella histicola bacteria are used.

[485] In some embodiments, the Prevotella histicola bacteria are administered to the subject before the additional therapeutic is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before). In some embodiments the Prevotella histicola bacteria are administered to the subject after the therapeutic is administered (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours after or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after). In some embodiments, the Prevotella histicola bacteria and the additional therapeutic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other). In some embodiments, the subject is administered an antibiotic before the Prevotella bacteria is administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days before). In some embodiments, the subject is administered an antibiotic after the Prevotella bacteria are administered to the subject (e.g., at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23 or 24 hours before or at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 or 30 days after). In some embodiments, the Prevotella bacteria and the antibiotic are administered to the subject simultaneously or nearly simultaneously (e.g., administrations occur within an hour of each other).

[486] In some aspects, antibiotics can be selected based on their bactericidal or bacteriostatic properties. Bactericidal antibiotics include mechanisms of action that disrupt the cell wall (e.g., P-lactams), the cell membrane (e.g., daptomycin), or bacterial DNA (e.g., fluoroquinolones). Bacteriostatic agents inhibit bacterial replication and include sulfonamides, tetracyclines, and macrolides, and act by inhibiting protein synthesis.

Furthermore, while some drugs can be bactericidal in certain organisms and bacteriostatic in others, knowing the target organism allows one skilled in the art to select an antibiotic with the appropriate properties. In certain treatment conditions, bacteriostatic antibiotics inhibit the activity of bactericidal antibiotics. Thus, in some embodiments, bactericidal and bacteriostatic antibiotics are not combined.

[487] Antibiotics include, but are not limited to aminoglycosides, ansamycins, carbacephems, carbapenems, cephalosporins, glycopeptides, lincosamides, lipopeptides, macrolides, monobactams, nitrofurans, oxazolidonones, penicillins, polypeptide antibiotics, quinolones, fluoroquinolone, sulfonamides, tetracyclines, and anti-mycobacterial compounds, and combinations thereof. [488] Aminoglycosides include, but are not limited to Amikacin, Gentamicin, Kanamycin, Neomycin, Netilmicin, Tobramycin, Paromomycin, and Spectinomycin. Aminoglycosides are effective, e.g., against Gram-negative bacteria, such as Escherichia coli, Klebsiella, Pseudomonas aeruginosa, and Francisella tularensis, and against certain aerobic bacteria but less effective against obligate/facultative anaerobes. Aminoglycosides are believed to bind to the bacterial 30S or 50S ribosomal subunit thereby inhibiting bacterial protein synthesis.

[489] Ansamycins include, but are not limited to, Geldanamycin, Herbimycin, Rifamycin, and Streptovaricin. Geldanamycin and Herbimycin are believed to inhibit or alter the function of Heat Shock Protein 90.

[490] Carbacephems include, but are not limited to, Loracarbef. Carbacephems are believed to inhibit bacterial cell wall synthesis.

[491] Carbapenems include, but are not limited to, Ertapenem, Doripenem, Imipenem/Cilastatin, and Meropenem. Carbapenems are bactericidal for both Grampositive and Gram-negative bacteria as broad-spectrum antibiotics. Carbapenems are believed to inhibit bacterial cell wall synthesis.

[492] Cephalosporins include, but are not limited to, Cefadroxil, Cefazolin, Cefalotin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil, and Ceftobiprole. Selected Cephalosporins are effective, e.g., against Gram-negative bacteria and against Grampositive bacteria, including Pseudomonas, certain Cephalosporins are effective against methicillin-resistant Staphylococcus aureus (MRSA). Cephalosporins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[493] Glycopeptides include, but are not limited to, Teicoplanin, Vancomycin, and Telavancin. Glycopeptides are effective, e.g., against aerobic and anaerobic Gram-positive bacteria including MRSA and Clostridium difficile. Glycopeptides are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[494] Lincosamides include, but are not limited to, Clindamycin and Lincomycin. Lincosamides are effective, e.g., against anaerobic bacteria, as well as Staphylococcus, and Streptococcus. Lincosamides are believed to bind to the bacterial 50S ribosomal subunit thereby inhibiting bacterial protein synthesis. [495] Lipopeptides include, but are not limited to, Daptomycin. Lipopeptides are effective, e.g., against Gram -positive bacteria. Lipopeptides are believed to bind to the bacterial membrane and cause rapid depolarization.

[496] Macrolides include, but are not limited to, Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Telithromycin, and Spiramycin. Macrolides are effective, e.g., against Streptococcus and Mycoplasma. Macrolides are believed to bind to the bacterial or 50S ribosomal subunit, thereby inhibiting bacterial protein synthesis.

[497] Monobactams include, but are not limited to, Aztreonam. Monobactams are effective, e.g., against Gram -negative bacteria. Monobactams are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[498] Nitrofurans include, but are not limited to, Furazolidone and Nitrofurantoin.

[499] Oxazolidonones include, but are not limited to, Linezolid, Posizolid, Radezolid, and Torezolid. Oxazolidonones are believed to be protein synthesis inhibitors.

[500] Penicillins include, but are not limited to, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cioxacillin, Dicloxacillin, Flucioxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Temocillin and Ticarcillin. Penicillins are effective, e.g., against Gram-positive bacteria, facultative anaerobes, e.g., Streptococcus, Borrelia, and Treponema. Penicillins are believed to inhibit bacterial cell wall synthesis by disrupting synthesis of the peptidoglycan layer of bacterial cell walls.

[501] Penicillin combinations include, but are not limited to, Amoxicillin/clavulanate, Ampicillin/sulbactam, Piperacillin/tazobactam, and Ticarcillin/clavulanate.

[502] Polypeptide antibiotics include, but are not limited to, Bacitracin, Colistin, and Polymyxin B and E. Polypeptide Antibiotics are effective, e.g., against Gram-negative bacteria. Certain polypeptide antibiotics are believed to inhibit isoprenyl pyrophosphate involved in synthesis of the peptidoglycan layer of bacterial cell walls, while others destabilize the bacterial outer membrane by displacing bacterial counter-ions.

[503] Quinolones and Fluoroquinolone include, but are not limited to, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, and Temafloxacin. Quinolones/Fluoroquinolone are effective, e.g., against Streptococcus and Neisseria. Quinolones/Fluoroquinolone are believed to inhibit the bacterial DNA gyrase or topoisomerase IV, thereby inhibiting DNA replication and transcription.

[504] Sulfonamides include, but are not limited to, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Trimethoprim-Sulfamethoxazole (Co-trimoxazole), and Sulfonamidochrysoidine. Sulfonamides are believed to inhibit folate synthesis by competitive inhibition of dihydropteroate synthetase, thereby inhibiting nucleic acid synthesis.

[505] Tetracyclines include, but are not limited to, Demeclocy cline, Doxycycline, Minocycline, Oxytetracycline, and Tetracycline. Tetracyclines are effective, e.g., against Gram-negative bacteria. Tetracyclines are believed to bind to the bacterial 30S ribosomal subunit thereby inhibiting bacterial protein synthesis.

[506] Anti-mycobacterial compounds include, but are not limited to, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, and Streptomycin.

[507] Suitable antibiotics also include arsphenamine, chloramphenicol, fosfomycin, fusidic acid, metronidazole, mupirocin, platensimycin, quinupristin/dalfopristin, tigecycline, tinidazole, trimethoprim amoxicillin/clavulanate, ampicillin/sulbactam, amphomycin ristocetin, azithromycin, bacitracin, buforin II, carbomycin, cecropin Pl, clarithromycin, erythromycins, furazolidone, fusidic acid, Na fusidate, gramicidin, imipenem, indolicidin, josamycin, magainan II, metronidazole, nitroimidazoles, mikamycin, mutacin B-Ny266, mutacin B-JH1 140, mutacin J-T8, nisin, nisin A, novobiocin, oleandomycin, ostreogrycin, piperacillin/tazobactam, pristinamycin, ramoplanin, ranalexin, reuterin, rifaximin, rosamicin, rosaramicin, spectinomycin, spiramycin, staphylomycin, streptogramin, streptogramin A, synergistin, taurolidine, teicoplanin, telithromycin, ticarcillin/clavulanic acid, triacetyloleandomycin, tylosin, tyrocidin, tyrothricin, vancomycin, vemamycin, and virginiamycin.

[508] In some embodiments, the additional therapeutic is an immunosuppressive agent, a DMARD, a pain-control drug, a steroid, a non-steroidal anti-inflammatory drug (NS AID), or a cytokine antagonist, and combinations thereof. Representative agents include, but are not limited to, cyclosporin, retinoids, corticosteroids, propionic acid derivative, acetic acid derivative, enolic acid derivatives, fenamic acid derivatives, Cox-2 inhibitors, lumiracoxib, ibuprophen, cholin magnesium salicylate, fenoprofen, salsalate, difunisal, tolmetin, ketoprofen, flurbiprofen, oxaprozin, indomethacin, sulindac, etodolac, ketorolac, nabumetone, naproxen, valdecoxib, etoricoxib, MK0966; rofecoxib, acetominophen, Celecoxib, Diclofenac, tramadol, piroxicam, meloxicam, tenoxicam, droxicam, lomoxicam, isoxicam, mefanamic acid, meclofenamic acid, flufenamic acid, tolfenamic, valdecoxib, parecoxib, etodolac, indomethacin, aspirin, ibuprophen, firocoxib, methotrexate (MTX), antimalarial drugs (e.g., hydroxychloroquine and chloroquine), sulfasalazine, Leflunomide, azathioprine, cyclosporin, gold salts, minocycline, cyclophosphamide, D-penicillamine, minocycline, auranofin, tacrolimus, myocrisin, chlorambucil, TNF alpha antagonists (e.g., TNF alpha antagonists or TNF alpha receptor antagonists), e.g., ADALIMUMAB (Humira®), ETANERCEPT (Enbrel®), INFLIXIMAB (Remicade®; TA-650), CERTOLIZUMAB PEGOL (Cimzia®; CDP870), GOLIMUMAB (Simpom®; CNTO 148), ANAKINRA (Kineret®), RITUXIMAB (Rituxan®; MabThera®), AB AT ACEPT (Orencia®), TOCILIZUMAB (RoActemra /Actemra®), integrin antagonists (TYSABRI® (natalizumab)), IL-1 antagonists (ACZ885 (Haris)), Anakinra (Kineret®)), CD4 antagonists, IL-23 antagonists, IL-20 antagonists, IL-6 antagonists, BLyS antagonists (e.g., Atacicept, Benlysta®/ LymphoStat-B® (belimumab)), p38 Inhibitors, CD20 antagonists (Ocrelizumab, Ofatumumab (Arzerra®)), interferon gamma antagonists (Fontolizumab), prednisolone, Prednisone, dexamethasone, Cortisol, cortisone, hydrocortisone, methylprednisolone, betamethasone, triamcinolone, beclometasome, fludrocortisone, deoxycorticosterone, aldosterone, Doxycycline, vancomycin, pioglitazone, SBI-087, SCIO- 469, Cura- 100, Oncoxin + Viusid, TwHF, Methoxsalen, Vitamin D - ergocalciferol, Milnacipran, Paclitaxel, rosig tazone, Tacrolimus (Prograf®), RADOO1, rapamune, rapamycin, fostamatinib, Fentanyl, XOMA 052, Fostamatinib disodium, rosightazone, Curcumin (Longvida™), Rosuvastatin, Maraviroc, ramipnl, Milnacipran, Cobiprostone, somatropin, tgAAC94 gene therapy vector, MK0359, GW856553, esomeprazole, everolimus, trastuzumab, JAK1 and JAK2 inhibitors, pan JAK inhibitors, e.g., tetracyclic pyridone 6 (P6), 325, PF-956980, denosumab, IL-6 antagonists, CD20 antagonistis, CTLA4 antagonists, IL-8 antagonists, IL-21 antagonists, IL-22 antagonist, integrin antagonists (Tysarbri® (natalizumab)), VGEF antagnosits, CXCL antagonists, MMP antagonists, defensin antagonists, IL-1 antagonists (including IL-1 beta antagonsits), and IL-23 antagonists (e.g., receptor decoys, antagonistic antibodies, etc.).

[509] In some embodiments, the additional therapeutic is an oral PDE4 inhibitor (such as apremilast). [510] In some embodiments, the additional therapeutic is apremilast, etanercept, infliximab, adalimumab, ustekinumab, dupilumab, or secukinumab.

[511] In some embodiments, the additional therapeutic is an immunosuppressive agent. Examples of immunosuppressive agents include, but are not limited to, corticosteroids, mesalazine, mesalamine, sulfasalazine, sulfasalazine derivatives, immunosuppressive drugs, cyclosporin A, mercaptopurine, azathiopurine, prednisone, methotrexate, antihistamines, glucocorticoids, epinephrine, theophylline, cromolyn sodium, antileukotrienes, anti-cholinergic drugs for rhinitis, TLR antagonists, inflammasome inhibitors, anti-cholinergic decongestants, mast-cell stabilizers, monoclonal anti-IgE antibodies, vaccines (e.g., vaccines used for vaccination where the amount of an allergen is gradually increased), cytokine inhibitors, such as anti-IL-6 antibodies, TNF inhibitors such as infliximab, adalimumab, certolizumab pegol, golimumab, or etanercept, and combinations thereof.

[512] In some embodiments, the additional therapeutic is an oral or injectable corticosteroid, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, a JAK inhibitor, tacrolimus, and/or leukotriene inhibitor.

[513] In some embodiments, the additional therapeutic is a topical corticosteroid, a topical calcineurin inhibitor (e.g., tacrolimus or pimecrolimus), or a topical PDE-4 inhibitor (e.g., crisaborole).

Administration

[514] In some embodiments, the bacterial composition is administered orally. In some embodiments, the administration to the subject once daily. In some embodiments, the administration to the subject twice daily. In some embodiments, the bacterial composition is administered in 2 or more doses (e.g., 3 or more, 4 or more or 5 or more doses). In some embodiments, the administration to the subject of the two or more doses are separated by at least 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 1 day, 2 days, 3 days, 4 days, 5 days, 6 days, 7 days, 8 days, 9 days, 10 days, 11 days, 12 days, 13 days, 14 days, 15 days, 16 days, 17 days, 18 days, 19 days, 20 days or 21 days.

[515] In some embodiments, the bacterial composition is administered once daily. In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[516] In some embodiments, the bacterial composition is administered twice daily. In some embodiments, the bacterial composition is administered twice daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered twice daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[517] In some embodiments, the bacterial composition is formulated as a tablet. In some embodiments, the bacterial composition is formulated as a capsule. In some embodiments, the bacterial composition comprises an enteric coating or micro encapsulation.

[518] In some embodiments, the subject is a mammal. In some embodiments, the subject is a human. In some embodiments, the subject is a non-human mammal (e.g., a dog, a cat, a cow, a horse, a pig, a donkey, a goat, a camel, a mouse, a rat, a guinea pig, a sheep, a llama, a monkey, a gorilla or a chimpanzee).

[519] In some embodiments of the methods provided herein, the bacterial composition is administered in conjunction with the administration of an additional therapeutic. In some embodiments, the bacterial composition comprises Prevotella bacteria co-formulated with the additional therapeutic. In some embodiments, the bacterial composition is coadministered with the additional therapeutic. In some embodiments, the additional therapeutic is administered to the subject before administration of the bacterial composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes before, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours before, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days before). In some embodiments, the additional therapeutic is administered to the subject after administration of the bacterial composition (e.g., about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 25, 30, 35, 40, 45, 50 or 55 minutes after, about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 or 23 hours after, or about 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13 or 14 days after). In some embodiments, the same mode of delivery is used to deliver both the bacterial composition and the additional therapeutic. In some embodiments, different modes of delivery are used to administer the bacterial composition and the additional therapeutic. For example, in some embodiments, the bacterial composition is administered orally while the additional therapeutic is administered via injection (e.g., an intravenous, and/or intramuscular injection). As another example, in some embodiments, a bacterial composition is administered orally while the additional therapeutic is administered topically.

[520] In some embodiments, the bacterial compositions, and dosage forms (e.g., solid dosage forms) described herein can be administered in conjunction with any other conventional treatment. These treatments may be applied as necessary and/or as indicated and may occur before, concurrent with or after administration of the bacterial compositions anddosage forms described herein.

[521] The dosage regimen can be any of a variety of methods and amounts, and can be determined by one skilled in the art according to known clinical factors. As is known in the medical arts, dosages for any one patient can depend on many factors, including the subject's species, size, body surface area, age, sex, immunocompetence, and general health, the therapeutic to be administered, duration and route of administration, the kind and stage of the disease, and other compounds such as an additional therapeutic being administered concurrently. In addition to the above factors, such levels can be affected by the infectivity of the microorganism, and the nature of the microorganism, as can be determined by one skilled in the art. In the present methods, appropriate minimum dosage levels of microorganisms can be levels sufficient for the microorganism to survive, grow and replicate. The dose of the bacterial compositions described herein may be appropriately set or adjusted in accordance with the dosage form, the route of administration, the degree or stage of a target disease, and the like.

[522] In some embodiments, the dose administered to a subject is sufficient to prevent disease (e.g., autoimmune disease, inflammatory disease, metabolic disease), or treat disease, e.g., delay its onset, ameliorate one or more symptom of the disease, lessen the severity of the disease (or a symptom thereof), or slow or stop its progression. One skilled in the art will recognize that dosage will depend upon a variety of factors including the strength of the particular compound employed, as well as the age, species, condition, and body weight of the subject. The size of the dose will also be determined by the route, timing, and frequency of administration as well as the existence, nature, and extent of any adverse side-effects that might accompany the administration of a particular compound and the desired physiological effect.

[523] In accordance with the above, in therapeutic applications (e.g., for treatment and/or prevention), the dosages of the additional therapeutic used in accordance with the methods disclosed herein vary depending on the active agent, the age, weight, and clinical condition of the recipient patient, and the experience and judgment of the clinician or practitioner administering the therapy, among other factors affecting the selected dosage.

[524] Separate administrations can include any number of two or more administrations, including two, three, four, five or six administrations. One skilled in the art can readily determine the number of administrations to perform or the desirability of performing one or more additional administrations according to methods known in the art for monitoring therapeutic methods and other monitoring methods provided herein. Accordingly, the methods provided herein include methods of providing to the subject one or more administrations of an additional therapeutic, where the number of administrations can be determined by monitoring the subject, and, based on the results of the monitoring, determining whether or not to provide one or more additional administrations. Deciding on whether or not to provide one or more additional administrations can be based on a variety of monitoring results.

[525] The time period between administrations can be any of a variety of time periods. The time period between administrations can be a function of any of a variety of factors, including monitoring steps, as described in relation to the number of administrations, the time period for a subject to mount an immune response. In one example, the time period can be a function of the time period for a subject to mount an immune response; for example, the time period can be more than the time period for a subject to mount an immune response, such as more than about one week, more than about ten days, more than about two weeks, or more than about a month; in another example, the time period can be less than the time period for a subject to mount an immune response, such as less than about one week, less than about ten days, less than about two weeks, or less than about a month.

[526] In some embodiments, the delivery of an additional therapeutic in combination with the bacterial composition described herein reduces the adverse effects and/or improves the efficacy of the additional therapeutic.

[527] The effective dose of an additional therapeutic described herein is the amount of the additional therapeutic that is effective to achieve the desired therapeutic response for a particular patient, composition, and mode of administration, with the least toxicity to the patient. The effective dosage level can be identified using the methods described herein and will depend upon a variety of pharmacokinetic factors including the activity of the particular compositions administered, the route of administration, the time of administration, the rate of excretion of the particular compound being employed, the duration of the treatment, other drugs, compounds and/or materials used in combination with the particular compositions employed, the age, sex, weight, condition, general health and prior medical history of the patient being treated, and like factors well known in the medical arts. In general, an effective dose of an additional therapeutic will be the amount of the additional therapeutic which is the lowest dose effective to produce a therapeutic effect. Such an effective dose will generally depend upon the factors described above.

[528] The toxicity of an additional therapeutic is the level of adverse effects experienced by the subject during and following treatment. Adverse events associated with additional therapeutic toxicity include, but are not limited to, abdominal pain, acid indigestion, acid reflux, allergic reactions, alopecia, anaphylaxis, anemia, anxiety, lack of appetite, arthralgias, asthenia, ataxia, azotemia, loss of balance, bone pain, bleeding, blood clots, low blood pressure, elevated blood pressure, difficulty breathing, bronchitis, bruising, low white blood cell count, low red blood cell count, low platelet count, cardiotoxicity, cystitis, hemorrhagic cystitis, arrhythmias, heart valve disease, cardiomyopathy, coronary artery disease, cataracts, central neurotoxicity, cognitive impairment, confusion, conjunctivitis, constipation, coughing, cramping, cystitis, deep vein thrombosis, dehydration, depression, diarrhea, dizziness, dry mouth, dry skin, dyspepsia, dyspnea, edema, electrolyte imbalance, esophagitis, fatigue, loss of fertility, fever, flatulence, flushing, gastric reflux, gastroesophageal reflux disease, genital pain, granulocytopenia, gynecomastia, glaucoma, hair loss, hand-foot syndrome, headache, hearing loss, heart failure, heart palpitations, heartburn, hematoma, hemorrhagic cystitis, hepatotoxicity, hyperamylasemia, hypercalcemia, hyperchloremia, hyperglycemia, hyperkalemia, hyperlipasemia, hypermagnesemia, hypernatremia, hyperphosphatemia, hyperpigmentation, hypertriglyceridemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypochloremia, hypoglycemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, impotence, infection, injection site reactions, insomnia, iron deficiency, itching, joint pain, kidney failure, leukopenia, liver dysfunction, memory loss, menopause, mouth sores, mucositis, muscle pain, myalgias, myelosuppression, myocarditis, neutropenic fever, nausea, nephrotoxicity, neutropenia, nosebleeds, numbness, ototoxicity, pain, palmar- plantar erythrodysesthesia, pancytopenia, pericarditis, peripheral neuropathy, pharyngitis, photophobia, photosensitivity, pneumonia, pneumonitis, proteinuria, pulmonary embolus, pulmonary fibrosis, pulmonary toxicity, rash, rapid heartbeat, rectal bleeding, restlessness, rhinitis, seizures, shortness of breath, sinusitis, thrombocytopenia, tinnitus, urinary tract infection, vaginal bleeding, vaginal dryness, vertigo, water retention, weakness, weight loss, weight gain, and xerostomia. In general, toxicity is acceptable if the benefits to the subject achieved through the therapy outweigh the adverse events experienced by the subject due to the therapy.

Immune disorders

[529] In some embodiments, the methods and compositions described herein relate to the treatment or prevention of a disease or disorder associated a pathological immune response, such as an autoimmune disease, an allergic reaction and/or an inflammatory disease. In some embodiments, the disease or disorder is an inflammatory bowel disease (e.g, Crohn’s disease or ulcerative colitis). In some embodiments, the disease or disorder is psoriasis (e.g, mild to moderate psoriasis). In some embodiments, the disease or disorder is atopic dermatitis (e.g., mild to moderate atopic dermatitis). In some embodiments, the disease or disorder is psoriatic arthritis.

[530] The methods described herein can be used to treat any subject in need thereof. As used herein, a “subject in need thereof’ includes any subject that has a disease or disorder associated with a pathological immune response (psoriasis (e.g., mild to moderate psoriasis) or atopic dermatitis (e.g., mild to moderate atopic dermatitis)) or psoriatic arthritis, as well as any subject with an increased likelihood of acquiring a such a disease or disorder.

[531] The compositions described herein can be used, for example, as a bacterial composition for preventing or treating (reducing, partially or completely, the adverse effects of) an autoimmune disease, such as chronic inflammatory bowel disease, systemic lupus erythematosus, psoriasis, psoriatic arthritis, muckle-wells syndrome, rheumatoid arthritis, multiple sclerosis, or Hashimoto's disease; an allergic disease, such as a food allergy, pollenosis, or asthma; an infectious disease, such as an infection with Clostridium difficile; an inflammatory disease such as a TNF-mediated inflammatory disease (e.g., an inflammatory disease of the gastrointestinal tract, such as pouchitis, a cardiovascular inflammatory condition, such as atherosclerosis, or an inflammatory lung disease, such as chronic obstructive pulmonary disease); a bacterial composition for suppressing rejection in organ transplantation or other situations in which tissue rejection might occur; a supplement, food, or beverage for improving immune functions; or a reagent for suppressing the proliferation or function of immune cells. [532] In some embodiments, the methods and compositions provided herein are useful for the treatment of inflammation (such as Thl, Th2 and/or Thl7 inflammation). In some embodiments, the inflammation of any tissue and organs of the body, including musculoskeletal inflammation, vascular inflammation, neural inflammation, digestive system inflammation, ocular inflammation, inflammation of the reproductive system, and other inflammation, as discussed below.

[533] Immune disorders of the musculoskeletal system include, but are not limited, to those conditions affecting skeletal joints, including joints of the hand, wrist, elbow, shoulder, jaw, spine, neck, hip, knew, ankle, and foot, and conditions affecting tissues connecting muscles to bones such as tendons. Examples of such immune disorders, which may be treated with the methods and compositions described herein include, but are not limited to, arthritis (including, for example, osteoarthritis, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, acute and chronic infectious arthritis, arthritis associated with gout and pseudogout, and juvenile idiopathic arthritis), tendonitis, synovitis, tenosynovitis, bursitis, fibrositis (fibromyalgia), epicondylitis, myositis, and osteitis (including, for example, Paget's disease, osteitis pubis, and osteitis fibrosa cystic).

[534] Ocular immune disorders refer to an immune disorder that affects any structure of the eye, including the eye lids. Examples of ocular immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, blepharitis, blepharochalasis, conjunctivitis, dacryoadenitis, keratitis, keratoconjunctivitis sicca (dry eye), scleritis, trichiasis, and uveitis.

[535] Examples of nervous system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, encephalitis, Guillain-Barre syndrome, meningitis, neuromyotonia, narcolepsy, multiple sclerosis, myelitis and schizophrenia. Examples of inflammation of the vasculature or lymphatic system which may be treated with the methods and compositions described herein include, but are not limited to, arthrosclerosis, arthritis, phlebitis, vasculitis, and lymphangitis.

[536] Examples of digestive system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, cholangitis, cholecystitis, enteritis, enterocolitis, gastritis, gastroenteritis, inflammatory bowel disease, ileitis, and proctitis. Inflammatory bowel diseases include, for example, certain art- recognized forms of a group of related conditions. Several major forms of inflammatory bowel diseases are known, with Crohn's disease (regional bowel disease, e.g., inactive and active forms) and ulcerative colitis (e.g., inactive and active forms) the most common of these disorders. In addition, the inflammatory bowel disease encompasses irritable bowel syndrome, microscopic colitis, lymphocytic-plasmocytic enteritis, coeliac disease, collagenous colitis, lymphocytic colitis and eosinophilic enterocolitis. Other less common forms of IBD include indeterminate colitis, pseudomembranous colitis (necrotizing colitis), ischemic inflammatory bowel disease, Behcet’s disease, sarcoidosis, scleroderma, IBD- associated dysplasia, dysplasia associated masses or lesions, and primary sclerosing cholangitis.

[537] Examples of reproductive system immune disorders which may be treated with the methods and compositions described herein include, but are not limited to, cervicitis, chorioamnionitis, endometritis, epididymitis, omphalitis, oophoritis, orchitis, salpingitis, tubo-ovarian abscess, urethritis, vaginitis, vulvitis, and vulvodynia.

[538] The methods and compositions described herein may be used to treat autoimmune conditions having an inflammatory component. Such conditions include, but are not limited to, acute disseminated alopecia universalise, Behcet's disease, Chagas' disease, chronic fatigue syndrome, dysautonomia, encephalomyelitis, ankylosing spondylitis, aplastic anemia, hidradenitis suppurativa, autoimmune hepatitis, autoimmune oophoritis, celiac disease, Crohn's disease, diabetes mellitus type 1, giant cell arteritis, good pasture's syndrome, Grave's disease, Guillain-Barre syndrome, Hashimoto's disease, Henoch- Schonlein purpura, Kawasaki's disease, lupus erythematosus, microscopic colitis, microscopic polyarteritis, mixed connective tissue disease, Muckle-Wells syndrome, multiple sclerosis, myasthenia gravis, opsoclonus myoclonus syndrome, optic neuritis, Ord’s thyroiditis, pemphigus, polyarteritis nodosa, polymyalgia, rheumatoid arthritis, Reiter's syndrome, Sjogren's syndrome, temporal arteritis, Wegener's granulomatosis, warm autoimmune haemolytic anemia, interstitial cystitis, Lyme disease, morphea, psoriasis, psoriatic arthritis, sarcoidosis, scleroderma, ulcerative colitis, and vitiligo.

[539] The methods and compositions described herein may be used to treat T-cell mediated hypersensitivity diseases having an inflammatory component. Such conditions include, but are not limited to, contact hypersensitivity, contact dermatitis (including that due to poison ivy), uticaria, skin allergies, respiratory allergies (hay fever, allergic rhinitis, house dustmite allergy) and gluten-sensitive enteropathy (Celiac disease).

[540] Other immune disorders which may be treated with the methods and compositions include, for example, appendicitis, dermatitis, dermatomyositis, endocarditis, fibrositis, gingivitis, glossitis, hepatitis, hidradenitis suppurativa, iritis, laryngitis, mastitis, myocarditis, nephritis, otitis, pancreatitis, parotitis, percarditis, peritonoitis, pharyngitis, pleuritis, pneumonitis, prostatistis, pyelonephritis, and stomatisi, transplant rejection (involving organs such as kidney, liver, heart, lung, pancreas (e.g., islet cells), bone marrow, cornea, small bowel, skin allografts, skin homografts, and heart valve xengrafts, sewrum sickness, and graft vs host disease), acute pancreatitis, chronic pancreatitis, acute respiratory distress syndrome, Sexary's syndrome, congenital adrenal hyperplasis, nonsuppurative thyroiditis, hypercalcemia associated with cancer, pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme, exfoliative dermatitis, seborrheic dermatitis, seasonal or perennial allergic rhinitis, bronchial asthma, contact dermatitis, atopic dermatitis, drug hypersensistivity reactions, allergic conjunctivitis, keratitis, herpes zoster ophthalmicus, iritis and oiridocyclitis, chorioretinitis, optic neuritis, symptomatic sarcoidosis, fulminating or disseminated pulmonary tuberculosis chemotherapy, idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) haemolytic anemia, leukaemia and lymphomas in adults, acute leukaemia of childhood, regional enteritis, autoimmune vasculitis, multiple sclerosis, chronic obstructive pulmonary disease, solid organ transplant rejection, sepsis. Exemplary treatments include treatment of transplant rejection, rheumatoid arthritis, psoriatic arthritis, multiple sclerosis, Type 1 diabetes, asthma, inflammatory bowel disease, systemic lupus erythematosis, psoriasis, psoriatic arthritis, chronic obstructive pulmonary disease, and inflammation accompanying infectious conditions e.g., sepsis).

[541] In some aspects, bacterial compositions for use of treating psoriasis are disclosed. In some aspects, a bacterial composition comprising Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) for use in treating psoriasis is described herein.

[542] In some aspects, uses of a bacterial composition for the preparation of a medicament for treating psoriasis (e.g., mild, moderate, or severe psoriasis or mild to moderate psoriasis) are disclosed. In some aspects, use of a bacterial composition for the preparation of a medicament for treating psoriasis wherein the bacterial composition comprises Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) is described herein. In some embodiments, the psoriasis is mild, moderate, or severe psoriasis. In some embodiments, the psoriasis is mild to moderate psoriasis.

[543] In some aspects, bacterial compositions for use of treating psoriatic arthritis are disclosed. In some aspects, a bacterial composition comprising Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) for use in treating psoriatic arthritis is described herein.

[544] In some aspects, uses of a bacterial composition for the preparation of a medicament for treating psoriatic arthritis are disclosed. In some aspects, use of a bacterial composition for the preparation of a medicament for treating psoriatic arthritis wherein the bacterial composition comprises Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) is described herein.

[545] In some aspects, bacterial compositions for use of treating atopic dermatitis are disclosed. In some aspects, a bacterial composition comprising Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) for use in treating atopic dermatitis is described herein.

[546] In some aspects, uses of a bacterial composition for the preparation of a medicament for treating atopic dermatitis (e.g., mild, moderate, or severe atopic dermatitis) are disclosed. In some aspects, use of a bacterial composition for the preparation of a medicament for treating atopic dermatitis wherein the bacterial composition comprises Prevotella histicola, wherein the Prevotella histicola is a strain comprising at least 85% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329) is described herein.

[547] Numerous embodiments are further provided that can be applied to any aspect of the methods and compositions described herein. For example, in some embodiments, the Prevotella histicola is a strain comprising at least 99.9% sequence identity to the nucleotide sequence of the Prevotella histicola Strain B 50329 (NRRL accession number B 50329). In some embodiments, the Prevotella histicola is the Prevotella histicola Strain B 50329 (NRRL accession number B 50329). In some embodiments, the bacterial composition is administered orally. In some embodiments, the bacterial composition is formulated as a tablet. In some embodiments, the bacterial composition is formulated as a capsule. [548] In some embodiments, the bacterial composition is administered once daily. In some embodiments, the bacterial composition is administered once daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered once daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the psoriasis is mild to moderate psoriasis. In some embodiments, the atopic dermatitis is mild, moderate, or severe atopic dermatitis.

[549] In some embodiments, the bacterial composition is administered twice daily. In some embodiments, the bacterial composition is administered twice daily for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the bacterial composition is administered twice daily for at least 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. In some embodiments, the psoriasis is mild to moderate psoriasis. In some embodiments, the atopic dermatitis is mild, moderate, or severe atopic dermatitis.

Metabolic Disorders

[550] In some embodiments, the methods and compositions described herein relate to the treatment or prevention of a metabolic disease or disorder a, such as type II diabetes, impaired glucose tolerance, insulin resistance, obesity, hyperglycemia, hyperinsulinemia, fatty liver, non-alcoholic steatohepatitis, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglylceridemia, ketoacidosis, hypoglycemia, thrombotic disorders, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), Nonalcoholic Steatohepatitis (NASH) or a related disease. In some embodiments, the related disease is cardiovascular disease, atherosclerosis, kidney disease, nephropathy, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, dermatopathy, dyspepsia, or edema. In some embodiments, the methods and compositions described herein relate to the treatment of Nonalcoholic Fatty Liver Disease (NAFLD) and Nonalcoholic Steatohepatitis (NASH).

[551] The compositions described herein can be used, for example, for preventing or treating (reducing, partially or completely, the adverse effects of) a metabolic disease, such as type II diabetes, impaired glucose tolerance, insulin resistance, obesity, hyperglycemia, hyperinsulinemia, fatty liver, non-alcoholic steatohepatitis, hypercholesterolemia, hypertension, hyperlipoproteinemia, hyperlipidemia, hypertriglylceridemia, ketoacidosis, hypoglycemia, thrombotic disorders, dyslipidemia, non-alcoholic fatty liver disease (NAFLD), Nonalcoholic Steatohepatitis (NASH), or a related disease. In some embodiments, the related disease is cardiovascular disease, atherosclerosis, kidney disease, nephropathy, diabetic neuropathy, diabetic retinopathy, sexual dysfunction, dermatopathy, dyspepsia, or edema.

Other Diseases and Disorders

[552] In some embodiments, the methods and compositions described herein relate to the treatment of liver diseases. Such diseases include, but are not limited to, Alagille Syndrome, Alcohol -Related Liver Disease, Alpha- 1 Antitrypsin Deficiency, Autoimmune Hepatitis, Benign Liver Tumors, Biliary Atresia, Cirrhosis, Galactosemia, Gilbert Syndrome, Hemochromatosis, Hepatitis A, Hepatitis B, Hepatitis C, Hepatic Encephalopathy, Intrahepatic Cholestasis of Pregnancy (ICP), Lysosomal Acid Lipase Deficiency (LAL-D), Liver Cysts, Liver Cancer, Newborn Jaundice, Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC), Reye Syndrome, Type I Glycogen Storage Disease, and Wilson Disease.

[553] The methods and compositions described herein may be used to treat neurodegenerative and neurological diseases. In some embodiments, the neurodegenerative and/or neurological disease is Parkinson’s disease, Alzheimer’s disease, prion disease, Huntington’s disease, motor neuron diseases (MND), spinocerebellar ataxia, spinal muscular atrophy, dystonia, idiopathicintracranial hypertension, epilepsy, nervous system disease, central nervous system disease, movement disorders, multiple sclerosis, encephalopathy, peripheral neuropathy or post-operative cognitive dysfunction.

Dysbiosis

[554] In recent years, it has become increasingly clear that the gut microbiome (also called the “gut microbiota”) can have a significant impact on an individual’s health through microbial activity and influence (local and/or distal) on immune and other cells of the host (Walker, W.A., Dysbiosis. The Microbiota in Gastrointestinal Pathophysiology. Chapter 25. 2017; Weiss and Thierry, Mechanisms and consequences of intestinal dysbiosis. Cellular and Molecular Life Sciences. (2017) 74(16):2959-2977. Zurich Open Repository and Archive, doi: https://doi.org/10.1007/s00018-017-2509-x)).

[555] A healthy host-gut microbiome homeostasis is sometimes referred to as a “eubiosis” or “normobiosis,” whereas a detrimental change in the host microbiome composition and/or its diversity can lead to an unhealthy imbalance in the microbiome, or a “dysbiosis” (Hooks and O’Malley. Dysbiosis and its discontents. American Society for Microbiology. Oct 2017. Vol. 8. Issue 5. mBio 8:e01492-17. https://doi.org/10.1128/mBio.01492-17). Dysbiosis, and associated local or distal host inflammatory or immune effects, may occur where microbiome homeostasis is lost or diminished, resulting in: increased susceptibility to pathogens; altered host bacterial metabolic activity; induction of host proinflammatory activity and/or reduction of host anti-inflammatory activity. Such effects are mediated in part by interactions between host immune cells (e.g., T cells, dendritic cells, mast cells, NK cells, intestinal epithelial lymphocytes (IEC), macrophages and phagocytes) and cytokines, and other substances released by such cells and other host cells.

[556] A dysbiosis may occur within the gastrointestinal tract (a “gastrointestinal dysbiosis” or “gut dysbiosis”) or may occur outside the lumen of the gastrointestinal tract (a “distal dysbiosis”). Gastrointestinal dysbiosis is often associated with a reduction in integrity of the intestinal epithelial barrier, reduced tight junction integrity and increased intestinal permeability. Citi, S. Intestinal Barriers protect against disease, Science

359: 1098-99 (2018); Srinivasan et al., TEER measurement techniques for in vitro barrier model systems. J. Lab. Autom. 20: 107-126 (2015). A gastrointestinal dysbiosis can have physiological and immune effects within and outside the gastrointestinal tract.

[557] The presence of a dysbiosis has been associated with a wide variety of diseases and conditions including: infection, cancer, autoimmune disorders (e.g., systemic lupus erythematosus (SLE)) or inflammatory disorders (e.g., functional gastrointestinal disorders such as inflammatory bowel disease (IBD), ulcerative colitis, and Crohn’s disease), neuroinflammatory diseases (e.g., multiple sclerosis), transplant disorders (e.g., graft- versus-host disease), fatty liver disease, type I diabetes, rheumatoid arthritis, Sjogren’s syndrome, celiac disease, cystic fibrosis, chronic obstructive pulmonary disorder (COPD), and other diseases and conditions associated with immune dysfunction. Lynch et al., The Human Microbiome in Health and Disease, N. Engl. J. Med .375:2369-79 (2016), Carding et al., Dysbiosis of the gut microbiota in disease. Microb. Ecol. Health Dis. (2015); 26: 10: 3402/mehd.v26.2619; Levy et al, Dysbiosis and the Immune System, Nature Reviews Immunology 17:219 (April 2017)

[558] Exemplary bacterial compositions disclosed herein can treat a dysbiosis and its effects by modifying the immune activity present at the site of dysbiosis. As described herein, such compositions can modify a dysbiosis via effects on host immune cells, resulting in, e.g., an increase in secretion of anti-inflammatory cytokines and/or a decrease in secretion of pro-inflammatory cytokines, reducing inflammation in the subject recipient or via changes in metabolite production.

[559] Exemplary bacterial compositions disclosed herein that are useful for treatment of disorders associated with a dysbiosis contain one or more types of immunomodulatory bacteria (e.g., anti-inflammatory bacteria) derived from such bacteria. Such compositions are capable of affecting the recipient host’s immune function, in the gastrointestinal tract, and/or a systemic effect at distal sites outside the subject’s gastrointestinal tract.

[560] Exemplary bacterial compositions disclosed herein that are useful for treatment of disorders associated with a dysbiosis contain a population of immunomodulatory bacteria of a single bacterial species (e.g., a single strain) (e.g., anti-inflammatory bacteria). Such compositions are capable of affecting the recipient host’s immune function, in the gastrointestinal tract, and /or a systemic effect at distal sites outside the subject’s gastrointestinal tract.

[561] In one embodiment, bacterial compositions containing an isolated population of immunomodulatory bacteria (e.g., anti-inflammatory bacterial cells) are administered (e.g., orally) to a mammalian recipient in an amount effective to treat a dysbiosis and one or more of its effects in the recipient. The dysbiosis may be a gastrointestinal tract dysbiosis or a distal dysbiosis.

[562] In another embodiment, bacterial compositions provided herein can treat a gastrointestinal dysbiosis and one or more of its effects on host immune cells, resulting in an increase in secretion of anti-inflammatory cytokines and/or a decrease in secretion of pro-inflammatory cytokines, reducing inflammation in the subject recipient.

[563] In another embodiment, the bacterial compositions can treat a gastrointestinal dysbiosis and one or more of its effects by modulating the recipient immune response via cellular and cytokine modulation to reduce gut permeability by increasing the integrity of the intestinal epithelial barrier.

[564] In another embodiment, the bacterial compositions can treat a distal dysbiosis and one or more of its effects by modulating the recipient immune response at the site of dysbiosis via modulation of host immune cells.

[565] Other exemplary bacterial compositions are useful for treatment of disorders associated with a dysbiosis, which compositions contain one or more types of bacteria capable of altering the relative proportions of host immune cell subpopulations, e.g., subpopulations of T cells, immune lymphoid cells, dendritic cells, NK cells and other immune cells, or the function thereof, in the recipient.

[566] Other exemplary bacterial compositions are useful for treatment of disorders associated with a dysbiosis, which compositions contain a population of immunomodulatory bacteria of a single bacterial species e.g., a single strain) capable of altering the relative proportions of immune cell subpopulations, e.g., T cell subpopulations, immune lymphoid cells, NK cells and other immune cells, or the function thereof, in the recipient subject.

[567] In one embodiment, provided herein are methods of treating a gastrointestinal dysbiosis and one or more of its effects by orally administering to a subject in need thereof a bacterial composition which alters the microbiome population existing at the site of the dysbiosis. The bacterial composition can contain one or more types of immunomodulatory bacteria or a population of immunomodulatory bacteria of a single bacterial species (e.g., a single strain).

[568] In one embodiment, provided herein are methods of treating a distal dysbiosis and one or more of its effects by orally administering to a subject in need thereof a bacterial composition which alters the subject’s immune response outside the gastrointestinal tract. The bacterial composition can contain one or more types of immunomodulatory bacteria or a population of immunomodulatory bacteria of a single bacterial species (e.g., a single strain).

[569] In exemplary embodiments, bacterial compositions useful for treatment of disorders associated with a dysbiosis stimulate secretion of one or more anti-inflammatory cytokines by host immune cells. Anti-inflammatory cytokines include, but are not limited to, IL- 10, IL-13, IL-9, IL-4, IL-5, TGFP, and combinations thereof. In other exemplary embodiments, bacterial compositions useful for treatment of disorders associated with a dysbiosis that decrease (e.g., inhibit) secretion of one or more pro-inflammatory cytokines by host immune cells. Pro-inflammatory cytokines include, but are not limited to, IFNy, IL-12p70, IL-la, IL-6, IL-8, MCP1, MIPla, MIPip, TNFa, and combinations thereof. Other exemplary cytokines are known in the art and are described herein.

[570] In another aspect, the provided herein is a method of treating or preventing a disorder associated with a dysbiosis in a subject in need thereof, comprising administering (e.g., orally administering) to the subject a bacterial composition in the form of a probiotic or medical food comprising bacteria an amount sufficient to alter the microbiome at a site of the dysbiosis, such that the disorder associated with the dysbiosis is treated.

[571] In another embodiment, a bacterial composition provided herein in the form of a probiotic or medical food may be used to prevent or delay the onset of a dysbiosis in a subject at risk for developing a dysbiosis.

Infection

[572] Inflammation can be a protective response to harmful stimuli, such as invading pathogens, damaged cells, toxic compounds, or cancerous cells. However, excessive inflammatory responses to such stimuli can result in serious adverse effects, including tissue damage and even death. For example, production of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1 beta (IL-1 P), and tumor necrosis factor alpha (TNFa) in response to many viral infections is one of the primary causes of the adverse symptoms associated with infection (including, in some cases, death). For example, release of inflammatory cytokines has been associated with disease severity resulting from infection by a number of viruses, including infection by coronaviruses (e.g., SARS-CoV-2, the virus that causes Coronavirus Disease 2019 (COVID-19)), influenza viruses, and respiratory syncytial viruses. For example, patients with severe COVID-19 often exhibit elevated levels of inflammatory cytokines in their lungs, which contributes to lung damage experienced by the COVID-19 patients.

[573] In some embodiments, the methods and compositions described herein relate to the treatment or prevention of bacterial septic shock, cytokine storm and/or viral infection.

[574] In some embodiments, the methods and compositions described herein relate to the treatment or prevention of a viral infection such as a respiratory viral infection, such as a coronavirus infection (e.g., a MERS (Middle East Respiratory Syndrome) infection, a severe acute respiratory syndrome (SARS) infection, such as a SARS-CoV-2 infection), an influenza infection, and/or a respiratory syncytial virus infection. In some embodiments, the methods and solid dosage forms described herein provided herein are for the treatment of a coronavirus infection (e.g., a MERS infection, a severe acute respiratory syndrome (SARS) infection, such as a SARS-CoV-2 infection). In some embodiments, provided herein are methods and solid dosage forms for treating COVID-19.

[575] In some embodiments, the methods and compositions described herein relate to the treatment or prevention of a viral infection. In some embodiments, the infection is a coronavirus infection, an influenza infection, and/or a respiratory syncytial virus infection. In some embodiments the viral infection is a SARS-CoV-2 infection.

[576] In some embodiments, an additional therapy is administered to the subject. In some embodiments, the additional therapy comprises an antiviral medication. In some embodiments, the additional therapy comprises an antiviral medication such as ribavirin, neuraminidase inhibitor, protease inhibitor, recombinant interferons, antibodies, oseltamivir, zanamivir, peramivir or baloxavir marboxil. In some embodiments, the additional therapy comprises hydroxychloroquine and/or chloroquine. In some embodiments, the additional therapy comprises remdesivir. In some embodiments, the additional therapy comprises plasma from a subject who has recovered from infection by the same virus that is infecting the subject (e.g., plasma from a subject who has recovered from SARS-CoV-2 infection). In some embodiments, the additional therapy comprises an anti-inflammatory agent such as NSAIDs or anti-inflammatory steroids. In some embodiments, the additional therapy comprises dexamethasone.

[577] In some embodiments, the additional therapy comprises an antibody specific for IL- 6 and/or the IL-6 receptor. In some embodiments, the additional therapy comprises tocilizumab (Actemra®). In some embodiments, the additional therapy comprises sarilumab (Kevzara®).

[578] In some embodiments, the additional therapy can comprise an anti-viral therapy. For example, the anti-viral therapy can comprise a nucleotide analog, such as remdesivir, galidesivir or clevudine; a viral RNA polymerase inhibitor such as favipiravir or galidesivir; a protease inhibitor such as ritonavir, darunavir, or danoprevir; an inhibitor of viral membrane fusion such as umifenovir; and/or anti-SARS-CoV-2 plasma.

[579] In some embodiments, the additional therapy can comprise an anti-inflammatory therapy. For example, the anti-inflammatory therapy can comprise a corticosteroid; sirolimus; anakinra; filamod; or an antibody. In some embodiments, the antibody can comprise a GMSF inhibitor, such as lenzilumab or gimsilumab; an anti-ILl beta inhibitor such as canakinumab; an IL-6 inhibitor such as tocilizumab or siltuximab; an IL-6R inhibitor such as sarilumab; and/or a CCR5 antagonist such as leronlimab.

[580] In some embodiments, the additional therapy can comprise a JAK inhibitor such as baricitinib, ruxolitinib, tofacitinib, and/or pacritinib.

[581] In some embodiments, the additional therapy can comprise a TLR7 agonist such as imiquimod or reisquimod. [582] In some embodiments, the additional therapy can comprise a cell-based therapy. For example, the cell-based therapy can comprise Remestemcel- L; bone marrow stem cell therapy, such as MultiStem or Bm-Allo-MSC; mesenchymal stromal cells; and/or adiopose derived mesenchymal stem cells such as AstroStem.

[583] In some embodiments, the additional therapy can comprise an ACE receptor inhibitor.

[584] In some embodiments, the additional therapy can comprise a regulator of the Sigma 1 and/or Sigma 2 receptor.

Exemplary Embodiments

[585] The present specification provides, among other things, the following exemplary embodiments:

[586] 1. A method of treating a condition in a human subject comprising orally administering to the human subject a dose of about 1.6 x IO¹⁰ cells to about 16 x 10¹¹ cells of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks.

[587] 2. The method of embodiment 1, wherein the condition comprises psoriasis, optionally wherein the psoriasis is mild, moderate, or severe psoriasis.

[588] 3. The method of embodiment 1, wherein the condition comprises atopic dermatitis, optionally wherein the atopic dermatitis is mild, moderate, or severe atopic dermatitis.

[589] 4. The method of embodiment 1, wherein the condition comprises psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis.

[590] 5. The method of embodiment 1, wherein the condition comprises an inflammatory disease.

[591] 6. The method of embodiment 5, the inflammatory disease is a Thl, Th2, or Thl7 inflammatory disease.

[592] 7. The method of embodiment 1, wherein the condition comprises an immune disorder.

[593] 8. The method of embodiment 1, wherein the condition comprises an autoimmune disease.

[594] 9. The method of embodiment 1, wherein the condition comprises a metabolic disease. [595] 10. The method of embodiment 1, wherein the condition comprises a dysbiosis.

[596] 11. The method of embodiment 1, wherein the condition comprises bacterial septic shock, cytokine storm and/or a viral infection.

[597] 12. The method of any one of embodiments 1-11, wherein the dose comprises about 8 x IO¹⁰ cells to about 8 x 10¹¹ cells.

[598] 13. The method of embodiment 12, wherein the dose comprises about 1.6 x 10¹¹ cells to about 6.4 x 10¹¹ cells.

[599] 14. The method of embodiment 12 or 13, wherein the dose comprises about 8 x IO¹⁰ cells.

[600] 15. The method of embodiment 12 or 13, wherein the dose comprises about 1.6 x 10¹¹ cells.

[601] 16. The method of embodiment 12 or 13, wherein the dose comprises about 6.4 x 10¹¹ cells.

[602] 17. The method of any one of embodiments 1 to 16, wherein the dose is administered to the subject once daily.

[603] 18. The method of any one of embodiments 1 to 16, wherein the dose is administered to the subject twice daily.

[604] 19. The method of any one of embodiments 1 to 18, wherein the dose is administered in combination with an additional therapy.

[605] 20. The method of any one of embodiments 1 to 19, wherein the dose is formulated in one or more solid dosage forms.

[606] 21. The method of embodiment 20, wherein the solid dosage form comprises about 8 x 10¹⁰ cells per solid dosage form.

[607] 22. The method of embodiment 20, wherein the solid dosage form comprises about 1.6 x 10¹¹ cells per solid dosage form.

[608] 23. The method of embodiment 20, wherein the solid dosage form comprises about 3.2 x 10¹¹ cells per solid dosage form.

[609] 24. The method of any one of embodiments 20 to 23, wherein one solid dosage form is administered to the subject once daily.

[610] 25. The method of any one of embodiments 20 to 23, wherein one solid dosage form is administered to the subject twice daily.

[611] 26. The method of any one of embodiments 20 to 23, wherein two solid dosage forms are administered to the subject once daily. [612] 27. The method of any one of embodiments 20 to 23, wherein two solid dosage forms are administered to the subject twice daily.

[613] 28. The method of embodiment 20 or 21, wherein two solid dosage forms are administered once daily, wherein each solid dose form comprises a dose of about 8 x IO¹⁰ total cells.

[614] 29. The method of embodiment 20 or 22, wherein two solid dosage forms are administered once daily, wherein each solid dosage form comprises a dose of about 1.6 x 10¹¹ total cells.

[615] 30. The method of embodiment 20 or 23, wherein two solid dosage forms are administered once daily, wherein each solid dosage form comprises a dose of about 3.2 x 10¹¹ total cells.

[616] 31. The method of embodiment 20 or 21, wherein one solid dosage form is administered once daily, wherein the solid dose form comprises a dose of about 8 x 10¹⁰ total cells.

[617] 32. The method of embodiment 20 or 22, wherein one solid dosage form is administered once daily, wherein the solid dosage form comprises a dose of about 1.6 x 10¹¹ total cells.

[618] 33. The method of embodiment 20 or 23, wherein one solid dosage form is administered once daily, wherein the solid dosage form comprises a dose of about 3.2 x 10¹¹ total cells.

[619] 34. The method of any one of embodiments 20 to 33, wherein the solid dosage form comprises a tablet or capsule.

[620] 35. The method of any one of embodiments 20 to 34, wherein the solid dosage form is enteric coated.

[621] 36. The method of any one of embodiments 20 to 35, wherein the one or more solid dosage forms are administered once daily for at least 36 weeks.

[622] 37. The method of any one of embodiments 20 to 35, wherein the one or more solid dosage forms are administered once daily for at least 48 weeks.

[623] 38. The method of any one of embodiments 20 to 35, wherein the one or more solid dosage forms are administered once daily for at least 52 weeks.

[624] 39. The method of any one of embodiments any one of embodiments 20 to 38, wherein the one or more solid dosage forms are administered in combination with an additional therapy. [625] 40. A method of treating psoriasis, optionally mild, moderate, or severe psoriasis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

[626] 41. The method of embodiment 40, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[627] 42. The method of embodiment 40, wherein solid dosage forms are administered once daily for at least 48 weeks.

[628] 43. The method of embodiment 40, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[629] 44. The method of any one of embodiments 40 to 43, wherein the solid dosage forms are administered in combination with an additional therapy.

[630] 45. A method of treating psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

[631] 46. The method of embodiment 45, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[632] 47. The method of embodiment 45, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[633] 48. The method of embodiment 45, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[634] 49. The method of any one of embodiments 45 to 48, wherein the solid dosage forms are administered in combination with an additional therapy.

[635] 50. A method of treating atopic dermatitis, optionally mild, moderate, or severe atopic dermatitis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria,

I l l wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

[636] 51. The method of embodiment 50, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[637] 52. The method of embodiment 50, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[638] 53. The method of embodiment 50, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[639] 54. The method of any one of embodiments 50 to 53, wherein the solid dosage forms are administered in combination with an additional therapy.

[640] 55. The method of any one of embodiments 50 to 54, wherein the solid dosage forms are administered in combination with an additional therapy, e.g., wherein the additional therapy comprises an emollient, optionally wherein the emollient comprises a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment, optionally wherein the emollient is used at least daily or at least twice daily.

[641] 56. A method of treating psoriasis, optionally mild, moderate, or severe psoriasis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

[642] 57. The method of embodiment 56, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[643] 58. The method of embodiment 56, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[644] 59. The method of embodiment 56, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[645] 60. The method of any one of embodiments 56 to 59, wherein the solid dosage forms are administered in combination with an additional therapy. [646] 61. A method of treating psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

[647] 62. The method of embodiment 61, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[648] 63. The method of embodiment 61, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[649] 64. The method of embodiment 61, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[650] 65. The method of any one of embodiments 61 to 64, wherein the solid dosage forms are administered in combination with an additional therapy.

[651] 66. A method of treating atopic dermatitis, optionally mild, moderate, or severe atopic dermatitis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

[652] 67. The method of embodiment 66, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[653] 68. The method of embodiment 66, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[654] 69. The method of embodiment 66, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[655] 70. The method of any one of embodiments 66 to 69, wherein the solid dosage forms are administered in combination with an additional therapy, e.g., wherein the additional therapy comprises an emollient, optionally wherein the emollient comprises a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment, optionally wherein the emollient is used at least daily or at least twice daily.

[656] 71. A method of treating inflammation in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 3.2 x 10¹¹ total cells of the bacteria , optionally wherein the solid dosage form is a tablet or a capsule.

[657] 72. The method of embodiment 71, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[658] 73. The method of embodiment 71, wherein the solid dosage forms are administered once daily for at least 48 weeks.

[659] 74. The method of embodiment 71, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[660] 75. The method of any one of embodiments 71 to 74, wherein the inflammation comprises Thl inflammation.

[661] 76. The method of any one of embodiments 71 to 74, wherein the inflammation comprises Th2 inflammation.

[662] 77 The method of any one of embodiments 71 to 74, wherein the inflammation comprises Thl7 inflammation.

[663] 78. The method of any one of embodiments 71 to 77, wherein the solid dosage forms are administered in combination with an additional therapy.

[664] 79. A method of treating inflammation in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

[665] 80. The method of embodiment 79, wherein the solid dosage forms are administered once daily for at least 36 weeks.

[666] 81. The method of embodiment 79, wherein the solid dosage forms are administered once daily for at least 48 weeks. [667] 82. The method of embodiment 79, wherein the solid dosage forms are administered once daily for at least 52 weeks.

[668] 83. The method of any one of embodiments 79 to 82, wherein the inflammation comprises Thl inflammation.

[669] 84. The method of any one of embodiments 79 to 82, wherein the inflammation comprises Th2 inflammation.

[670] 85. The method of any one of embodiments 79 to 82, wherein the inflammation comprises Thl7 inflammation.

[671] 86. The method of any one of embodiments 79 to 85, wherein the solid dosage forms are administered in combination with an additional therapy.

[672] 87. A method of treating psoriasis, optionally mild, moderate, or severe psoriasis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

[673] 88. The method of embodiment 87, wherein the solid dosage form is administered once daily for at least 36 weeks.

[674] 89. The method of embodiment 87, wherein the solid dosage form is administered once daily for at least 48 weeks.

[675] 90. The method of embodiment 87, wherein the solid dosage form is administered once daily for at least 52 weeks.

[676] 91. The method of any one of embodiments 87 to 90, wherein the solid dosage form is administered in combination with an additional therapy.

[677] 92. A method of treating psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule. [678] 93. The method of embodiment 92, wherein the solid dosage form is administered once daily for at least 36 weeks.

[679] 94. The method of embodiment 92, wherein the solid dosage form is administered once daily for at least 48 weeks.

[680] 95. The method of embodiment 92, wherein the solid dosage form is administered once daily for at least 52 weeks.

[681] 96. The method of any one of embodiments 92 to 95, wherein the solid dosage form is administered in combination with an additional therapy.

[682] 97. A method of treating atopic dermatitis, optionally mild, moderate, or severe atopic dermatitis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

[683] 98. The method of embodiment 97, wherein the solid dosage form is administered once daily for at least 36 weeks.

[684] 99. The method of embodiment 97, wherein the solid dosage form is administered once daily for at least 48 weeks.

[685] 100. The method of embodiment 97, wherein the solid dosage form is administered once daily for at least 52 weeks.

[686] 101. The method of any one of embodiments 97 to 100, wherein the solid dosage forms are administered in combination with an additional therapy, e.g., wherein the additional therapy comprises an emollient, optionally wherein the emollient comprises a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment, optionally wherein the emollient is used at least daily or at least twice daily.

[687] 102. A method of treating inflammation in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule. [688] 103. The method of embodiment 102, wherein the solid dosage form is administered once daily for at least 36 weeks.

[689] 104. The method of embodiment 102, wherein the solid dosage form is administered once daily for at least 48 weeks.

[690] 105. The method of embodiment 102, wherein the solid dosage form is administered once daily for at least 52 weeks.

[691] 106. The method of any one of embodiments 102 to 105, wherein the inflammation comprises Thl inflammation.

[692] 107. The method of any one of embodiments 102 to 105, wherein the inflammation comprises Th2 inflammation.

[693] 108. The method of any one of embodiments 102 to 105, wherein the inflammation comprises Th 17 inflammation.

[694] 109. The method of any one of embodiments 102 to 108, wherein the solid dosage form is administered in combination with an additional therapy.

EXAMPLES

Example 1: Prevotella histicola Strain B Treatment for Mild to Moderate Psoriasis

[695] Psoriasis is a chronic immune-mediated type 1/3 (Thl/Thl7) inflammatory skin disease in which hyperactive T cells trigger excessive keratinocyte proliferation. This results in the formation of raised erythematous plaques with scaling. Psoriatic lesions can appear anywhere on the body but are most often seen on the knees, elbows, scalp, and lumbar area. Critical events in the inflammatory process include activation of Langerhans cells and T cells, selective trafficking of activated T cells to the skin, and induction of an inflammatory cytokine and chemokine cascade in skin lesions. Clinical data have validated the role of anti-TNFa, anti-IL-17, and anti-IL-23 therapy in moderate to severe psoriasis. For patients with mild to moderate psoriasis, therapy usually involves topical agents (topical corticosteroids, vitamin D3 analogs), with topical corticosteroids providing the greatest range of efficacy and a wide range of formulations. More recently, physicians are prescribing apremilast, a first-in-class oral PDE4 inhibitor, ahead of biological therapy, which includes etanercept, infliximab, adalimumab, ustekinumab, and secukinumab.

[696] Prevotella histicola Strain B can be used for the treatment of psoriasis, e.g., at the doses and dosing regimens provided herein. The psoriasis can be mild, moderate, or severe psoriasis. Dose:

[697] Cohort: 8 x 1O¹⁰ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[698] Cohort: 1.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[699] Cohort: 3.2 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[700] Cohort: 6.4 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[701] Cohort: 8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[702] Cohort: 9.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[703] Cohort: 12.8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

Efficacy Assessments:

[704] The following endpoints can be evaluated prior to first administration of a bacterial composition described herein, and/or at intervals during administration (e.g., 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks) of a bacterial composition described herein and/or after administration has terminated (e.g., 2 and/or 4 and/or 24 weeks after termination):

Psoriasis Area and Severity Index Score

[705] The PASI score will be assessed as described by Langley and Ellis (2004). The PASI is a physician assessment that combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease). The absolute PASI score in this study is used as part of inclusion criterion #4. The PASI percentage response rates are efficacy endpoints (i.e., PASI-50, PASI-75, PASI-90, and PASI-100). For example, the percentage of participants who achieve a 75% or greater reduction in PASI score from baseline is represented by the PASI-75 value. Details of the PASI assessment will be provided in the study manual.

Lesion Severity Score

[706] The LSS is used to score the severity of psoriasis plaques (Patel and Tsui 2011). The dimensions of scaling, erythema, and plaque elevation are each scored on a scale from 0 to 4, and the total LSS is the numerical sum of the 3-dimensional scores observed at a single study visit.

Physician’s Global Assessment

[707] The National Psoriasis Foundation Psoriasis Score version of a static PGA is calculated by averaging the total body erythema, induration, and desquamation scores (Feldman and Krueger 2005). Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores. Details of the PGA assessment will be provided in the study manual.

Percent of Body Surface Area Involvement

[708] The percent of BSA involvement will be estimated for each participant, where 1% is approximately the area of the participant’s handprint (Walsh et al 2013). Details of the BSA assessment will be provided in the study manual.

[709] Walsh and colleagues proposed the product of the PGA and the BSA involvement as a simple and effective alternative for measuring severity of psoriasis in clinical trials (Walsh et al 2013).

Modified Nail Psoriasis Severity Index

[710] The mNAPSI is a numeric, reproducible, objective, and simple tool for physicians to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit (Cassell et al 2007). Details of conducting the mNAPSI will be provided in the study manual. Dermatology Life Quality Index

[711] The DLQI is a patient reported outcomes instrument for assessing the impact of dermatologic conditions on patients’ quality of life (Finlay and Khan 1994). Details of administering the DLQI will be provided in the study manual.

Psoriasis Symptom Inventory

[712] The PSI is a patient reported outcomes instrument that is used to assess the severity of plaque psoriasis symptoms (Bushnell et al 2013). All symptoms (itch, redness, scaling, burning, cracking, stinging, flaking, and pain) are rated on a 5-point severity scale. The PSI demonstrated good construct validity and was sensitive to within-subject change (p<0.0001). Details of administering the PSI will be provided in the study manual.

Pain

[713] Pain will be assessed by the SF-36 Bodily Pain Scale (SF-36 BPS) and the VAS Pain (Hawker et al 2011). Details of administering the pain assessments will be provided in the study manual.

Fatigue

[714] Consistent with a recent study of fatigue in psoriasis (Skoie et al 2017), fatigue will be assessed by the vitality subscale of the SF-36 (van der Heijden et al 2003) and a fatigue VAS (Wolfe 2004). Details of administering the fatigue assessments will be provided in the study manual.

Histologic Assessment

[715] Standard histology will be performed on skin plaque biopsies (including epidermal thickness, basal mitotic counts and immune cell infiltrates, immunohistochemistry). mRNA Transcription Analysis

[716] An mRNA transcription analysis will be performed on the skin plaque biopsies.

Blood Cytokine and Chemokine Analysis

[717] Blood samples will be stimulated ex vivo and analyzed for levels of cytokines and chemokines, including IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL- 10, IL-12p40, IL- 17 A, TNFa, and fFNy. References

Blake MR, Raker JM, Whelan K. Validity and reliability of the Bristol Stool Form Scale in healthy adults and patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther. 2016;44:693-703.

Bornkamp B. Practical considerations for using functional uniform prior distributions for dose-response estimation in clinical trials. Biom J. 2014;56(6):947-62.

Bushnell DM, Martin ML, McCarrier K, et al. Validation of the Psoriasis Symptom Inventory (PSI), a patient-reported outcome measure to assess psoriasis symptom severity. J Dermatolog Treat. 2013;24(5):356-60.

Cassell SE, Bieber JD, Rich P, et al. The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis. J Rheumatol. 2007 Jan;34(l): 123-9. de Groot PF, Belzer C, Aydin 0, et al. Distinct fecal and oral microbiota composition in human type 1 diabetes, an observational study. PLoS One. 2017;12(12):e0188475.

Feldman SR, Krueger GG. Psoriasis assessment tools in clinical trials. Ann Rheum Dis. 2005;64(Suppl 2):ii65-8; discussion ii69-73.

Felix KM, Tahsin S, Wu HJ. Host-microbiota interplay in mediating immune disorders. Ann N Y Acad Sci. 2018;1417(l):57-70.

Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure for routine clinical use. Clin Exp Dermatol. 1994;19:210-6.

Hawker GA, Mian S, Kendzerska T, et al. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken). 2011;63 Suppl 1 ES240-52.

Hindson J. Multiple sclerosis: A possible link between multiple sclerosis and gut microbiota. Nat Rev Neurol. 2017;13(12):705.

Human Microbiome Project Consortium. A framework for human microbiome research. Nature. 2012;486:215-21. Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment. J Am Acad Dermatol. 2004;51(4):563-9.

Mangalam A, Shahi SK, Luckey D, et al. Human gut-derived commensal bacteria suppress CNS inflammatory and demyelinating disease. Cell Rep. 2017;20(6): 1269-77.

Marietta EV, Murray JA, Luckey DH, et al. Human gut-derived Prevotella histicola suppresses inflammatory arthritis in humanized mice. Arthritis Rheumatol.

2016;68(12):2878-88.

O’Donnell LJD, Virjee J, Heaton KW. Detection of pseudodiarrhoea by simple clinical assessment of intestinal transit rate. BMJ. 1990;300:439-40.

Patel RV, Tsui CL. Evaluating psoriasis: a review of the assessments most commonly used in clinical trials. Psoriasis Forum. 2011;17(4):259-66. doi: 10.1177/247553031117a00403.

Skoie IM, Dalen I, Temowitz T, et al. Fatigue in psoriasis: a controlled study. Br J Dermatol. 2017;177(2):505-12.

Spiegelhalter DJ, Abrams KR, Myles JP. Bayesian approaches to clinical trials and healthcare evaluation. Chichester: John Wiley and Sons Ltd; 2004. 408 p. van der Heijden PG, van Buuren S, Fekkes M, et al. Unidimensionality and reliability under Mokken scaling of the Dutch language version of the SF-36. Qual Life Res. 2003;12: 189- 98.

Vandeputte D, Falony G, Vieira-Silva S, et al. Stool consistency is strongly associated with gut microbiota richness and composition, enterotypes and bacterial growth rates. Gut. 2016;65:57-62.

Vandeputte D, Kathagen G, D’hoe K, et al. Quantitative microbiome profiling links gut community variation to microbial load. Nature. 2017;551 :507-11.

Walsh JA, McFadden M, Woodcock J, et al. Product of the Physician Global Assessment and body surface area: a simple static measure of psoriasis severity in a longitudinal cohort. J Am Acad Dermatol. 2013;69(6):931-7.

Wolfe F. Fatigue assessments in rheumatoid arthritis: comparative performance of visual analog scales and longer fatigue questionnaires in 7760 patients. J Rheumatol.

2004;31(10): 1896-902. Yan D, Issa N, Afifi L, et al. The role of the skin and gut microbiome in psoriatic disease.

Curr Dermatol Rep. 2017;6:94-103.

Example 2: Additional Psoriasis Read-Outs

[718] Prevotella histicola Strain B can be used for the treatment of psoriasis, e.g., at the doses and dosing regimens provided herein. The psoriasis can be mild, moderate, or severe psoriasis.

Dose:

[719] Cohort: 8 x 1O¹⁰ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 420, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[720] Cohort: 1.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[721] Cohort: 3.2 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[722] Cohort: 6.4 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[723] Cohort: 8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[724] Cohort: 9.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[725] Cohort: 12.8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriasis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

Endpoints:

[726] The effects of Prevotella histicola Strain B on psoriasis can be optionally evaluated by one or more of the following criteria, e.g., at week 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 and/or 2, 4, and/or 24 weeks after treatment: • Mean percentage change from baseline in the product of sPGA and BSA (total psoriasis severity index)

• Mean absolute and percentage change from baseline in the product of sPGA and BSA

• Mean absolute and percentage change from baseline in PASI

• Percentage of patients achieving at least a 50% improvement in PASI from baseline (PASI50)

• Time to achieve PASI50

• Percentage of patients achieving at least a 75% improvement in PASI from baseline (PASI75)

• Time to achieve PASI75

• Percentage of patients with a sPGA of clear (0) or very mild (1)

• Time to achieve sPGA of 0 or 1

• Percentage of patients with a sPGA of clear (0) or very mild (1) with a >2 point improvement from baseline

• Absolute and Percentage change from baseline in total BSA affected by psoriasis

• Absolute and Percentage change from baseline in total PSI score

• Absolute and Percentage change from baseline in total DLQI (subjects aged >1_8_)_ or cDLQI (subjects aged <18) score

• Percentage of subjects achieving an improvement from baseline of 4 or more in the DLQI

• Absolute and Percentage change from baseline in Pruritus-NRS

• Change from baseline in mNAPSI score

• Change from baseline in Psoriasis scalp severity index (PSSI) score

• EQ-5D (version 3L for subjects aged >18; and version Y for subjects aged

12 to <18)

• Treatment Satisfaction Questionnaire for Medication (TSQM)

• Hospital Anxiety and Depression Scale (HADS) (subjects aged >18), or the Paediatric Index of Emotional Distress (PLED) (subjects aged 12 to <18)

• Decrease in pain, e.g., as assessed by the SF-36 Bodily Pain Scale and/or the VAS Pain assessment • Decrease in fatigue, e.g., as assessed by the vitality subscale of SF-36 and/or a fatigue VAS

[727] Efficacy assessments can include one or more of: the PASI score, the LSS, the National Psoriasis Foundation Psoriasis Score version of a static PGA, the percent of BSA involvement, the mNAPSI, the DLQI, the PSI (Psoriasis Symptom Inventory).

[728] Psoriasis Area and Severity Index Score: The PASI score can be assessed as described by Langley and Ellis (2004). The PASI is a physician assessment that combines the assessment of the severity of and area affected by psoriasis into a single score in the range 0 (no disease) to 72 (maximal disease). The PASI percentage response rates are efficacy endpoints (i.e., PASI-50, PASI-75, PASI-90, and PASI-100). For example, the percentage of participants who achieve a 75% or greater reduction in PASI score from baseline is represented by the PASI-75 value.

[729] Lesion Severity Score: The LSS is used to score the severity of psoriasis plaques (Patel and Tsui 2011). The dimensions of scaling, erythema, and plaque elevation are each scored on a scale from 0 to 4, and the total LSS is the numerical sum of the 3-dimensional scores observed at a single study visit.

[730] Physician ’s Global Assessment: The National Psoriasis Foundation Psoriasis Score version of a static PGA is calculated by averaging the total body erythema, induration, and desquamation scores (Feldman and Krueger 2005). Erythema, induration, and desquamation will be scored on a 6-point scale, ranging from 0 (clear) to 5 (severe): the total PGA score is defined as the average of the erythema, induration, and desquamation scores.

[731] Percent of Body Surface Area Involvement: The percent of BSA involvement can be estimated for each participant, where 1% is approximately the area of the participant’s handprint (Walsh et al 2013).

[732] Walsh and colleagues proposed the product of the PGA and the BSA involvement as a simple and effective alternative for measuring severity of psoriasis in clinical trials (Walsh et al 2013).

[733] Modified Nail Psoriasis Severity Index: The mNAPSI is a numeric, reproducible, objective, and simple tool for physicians to evaluate the severity of nail bed psoriasis and nail matrix psoriasis by area of involvement in the nail unit (Cassell et al 2007). [734] Dermatology Life Quality Index: The DLQI is a patient reported outcomes instrument for assessing the impact of dermatologic conditions on patients’ quality of life (Finlay and Khan 1994).

[735] Psoriasis Symptom Inventory: The PSI is a patient reported outcomes instrument that is used to assess the severity of plaque psoriasis symptoms (Bushnell et al 2013). All symptoms (itch, redness, scaling, burning, cracking, stinging, flaking, and pain) are rated on a 5-point severity scale. The PSI demonstrated good construct validity and was sensitive to wi thin-subject change (p<0.0001).

[736] Pain: Pain can be assessed by the SF-36 Bodily Pain Scale (SF-36 BPS) and the VAS Pain (Hawker et al 2011).

[737] Fatigue: Consistent with a recent study of fatigue in psoriasis (Skoie et al 2017), fatigue can be assessed by the vitality subscale of the SF-36 (van der Heijden et al 2003) and a fatigue VAS (Wolfe 2004).

[738] In embodiments, provided herein is a method of treating psoriasis comprising administering (e.g., orally administering) to a human subject a Prevotella histicola strain and/or a composition (e.g., a bacterial composition and/or a solid dosage form) comprising a strain of Prevotella histicola provided herein. In some embodiments, the human subject has a confirmed diagnosis of mild to moderate plaque-type psoriasis for at least 6 months involving no more than 10% of body surface area (BSA) (excluding the scalp). In some embodiments, the human subject has a minimum of 2 psoriatic lesions. In some embodiments, the subject has not received systemic non-biologic psoriasis therapy (methotrexate [MTX], steroids, cyclophosphamide) or psoralen plus ultraviolet A (PUVA)/ultraviolet A (UVA) phototherapy within 4 weeks prior to dosing. In some embodiments, subject has not received treatment with biologic agents within 12 months prior to first dose. In some embodiments, the subject is not continuing use of topical or oral pharmacologically active agents 2 weeks prior to the start of dosing. In some embodiments, the human subject has a documented diagnosis of plaque psoriasis for >6 months.

[739] In some embodiments, the human subject has had mild to moderate plaque psoriasis with plaque covering BSA of >3% and <10% and meet both of the following additional criteria: (i) PASI score of >6 and <15, and (ii) PGA score of 2 or 3.

[740] In some embodiments, the method decreases the PASI (Psoriasis Area and Severity Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PASI score prior to the commencement of treatment).

[741] In some embodiments, the method increases a PASI percentage response rate (e.g., PASI-50, PASI-75, PASI-90, or PASI-100), e.g., as described herein. For example, the percentage of subjects who achieve a 75% or greater reduction in PASI score from baseline is represented by the PASI-75 value, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment.

[742] In some embodiments, the method decreases the LSS (Lesion Severity Score) in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s LSS prior to the commencement of treatment), e.g., as described herein.

[743] In some embodiments, the method decreases the PGA (Physician’s Global Assessment) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PGA score prior to the commencement of treatment), e.g., as described herein.

[744] In some embodiments, the method decreases the percent of BSA (Body Surface Area) involvement in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s percent involvement prior to the commencement of treatment), e.g., as described herein.

[745] In some embodiments, the method decreases the mNAPSI (Modified Nail Psoriasis Severity Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s mNAPSI score prior to the commencement of treatment), e.g., as described herein.

[746] In some embodiments, the method improves the DLQI (Dermatology Life Quality Index) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s DLQI score prior to the commencement of treatment), e.g., as described herein.

[747] In some embodiments, the method improves the PSI (Psoriasis Symptom Inventory) score in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s PSI score prior to the commencement of treatment), e.g., as described herein.

[748] In some embodiments, the method decreases pain in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s pain prior to the commencement of treatment), e.g., as described herein. For example, pain can be assessed by the SF-36 Bodily Pain Scale (SF-36 BPS) or the VAS Pain.

[749] In some embodiments, the method decreases fatigue in the subject, e.g., after 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks of treatment (e.g., as compared to the subject’s fatigue prior to the commencement of treatment), e.g., as described herein.

References:

Cassell SE, Bieber JD, Rich P, et al. The modified Nail Psoriasis Severity Index: validation of an instrument to assess psoriatic nail involvement in patients with psoriatic arthritis. J Rheumatol. 2007 Jan;34(l): 123-9.

Langley RG, Ellis CN. Evaluating psoriasis with Psoriasis Area and Severity Index, Psoriasis Global Assessment, and Lattice System Physician's Global Assessment. J Am Acad Dermatol. 2004;51(4):563-9.

Skoie IM, Dalen I, Temowitz T, et al. Fatigue in psoriasis: a controlled study. Br J Dermatol. 2017;177(2):505-12. van der Heijden PG, van Buuren S, Fekkes M, et al. Unidimensionality and reliability under Mokken scaling of the Dutch language version of the SF-36. Qual Life Res. 2003;12: 189- 98.

2004;31(10): 1896-902.

Example 3: Prevotella histicola Strain B Treatment for Atopic Dermatitis

[750] Prevotella histicola Strain B can be used for the treatment of atopic dermatitis, e.g., at the doses and dosing regimens provided herein. The atopic dermatitis can be mild, moderate, or severe atopic dermatitis. The atopic dermatitis can be mild to moderate atopic dermatitis.

Dose:

[751] Cohort: 8 x 1O¹⁰ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[752] Cohort: 1.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[753] Cohort: 3.2 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[754] Cohort: 6.4 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[755] Cohort: 8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. [756] Cohort: 9.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[757] Cohort: 12.8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with atopic dermatitis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

Efficacy Assessments:

[758] The following endpoints can be evaluated at intervals prior to first administration of a bacterial composition described herein, and/or during administration (e.g., 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks) of a bacterial composition described herein and/or after administration has terminated (e.g., 2 and/or 4 and/or 24 weeks after termination):

EASI

[759] The Eczema Area and Severity Index (EASI) is a validated measure of eczema severity, which takes into account a combination of the body surface area affected, and the severity of erythema, oedema, excoriation and lichenification. The EASI score ranges from 0 - 72. (EASI, 2017) EASI-50 and EASI-75 responses are defined as at least 50% and 75% decrease from baseline EASI score respectively.

SCORAD

[760] The SCORing Atopic Dermatitis (SCORAD) is a clinical tool which is also used to assess the extent and severity of eczema, to assess treatment effects (ETFAD, 1993). As well as an investigator-rated area and disease intensity score, there is a subjective symptoms component which takes into account itch and sleeplessness using a visual analogue scale. The SCORAD score ranges from 0 - 103.

BSA

[761] The Body Surface Area (BSA) is a measure of the extent of atopic dermatitis at a given time. It is calculated by estimating the number of participant’s handprints of active atopic dermatitis are present; where one handprint (including digits) represents 1% body surface area.

IGA

[762] The Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA- AD) will be used to describe the overall appearance of lesions, at a given time-point (Simpson, 2020). There is a standardized grading system. In indeterminate cases, extent will be used to differentiate between scores - but otherwise extent is not used in the scoring system. The IGA score ranges from 0 (Clear) to 4 (Severe).

IGA x BSA

[763] The product of the IGA and BSA provides a simple but useful measure of the extent and severity of eczema that is commonly used in the clinical trial setting.

DLQI questionnaire

[764] This is a validated patient reported outcomes instrument which asks 10 questions to assess how a participant’s skin disease has affected their quality of life over the past week (Finlay, 1994). The DLQI score ranges from 0 to 30.

POEM questionnaire

[765] The Patient-Orientated Eczema Measure (POEM) includes 7 questions about the participant’s atopic dermatitis. Each of the 7 questions is scored from 0 to 4, giving a POEM score range from 0 to 28.

Pruritus NRS questionnaire

[766] The Pruritus Numerical Rating Scale (Pruritus-NRS) is a 10-point scale for participants to rate both their average and worst itch that they have experienced over the previous 24 hours.

Example 4: Prevotella histicola Strain B for the Treatment of Psoriatic Arthritis

[767] Prevotella histicola Strain B can be used for the treatment of psoriatic arthritis (PsA), e.g., at the doses and dosing regimens provided herein. The psoriatic arthritis can be mild, moderate, or severe psoriatic arthritis.

Dose:

[768] Cohort: 8 x 1O¹⁰ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[769] Cohort: 1.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[770] Cohort: 3.2 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks. [771] Cohort: 6.4 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[772] Cohort: 8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[773] Cohort: 9.6 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

[774] Cohort: 12.8 x 10¹¹ cells of Prevotella Strain B 50329 or matching placebo administered as capsules or tablets, once daily to subjects with psoriatic arthritis for 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 weeks.

Endpoints:

[775] The effects of Prevotella histicola Strain B on psoriatic arthritis can be evaluated by one or more of the following criteria e.g., at week 20, 24, 28, 32, 36, 40, 44, 48, 52, or 56 and/or 2, 4, and/or 24 weeks after treatment:

[776] Percentage of patients with an ACR20, ACR50, and/or ACR70 response: The ACR (American College of Rheumatology) is a standard criteria originally developed to measure the effectiveness of various arthritis medications or treatments in clinical trials for rheumatoid arthritis, but is also widely used in PsA. The ACR measures improvement in tender joint count (TJC) or swollen joint count (SJC), and improvement in at least 3 of the following 5 parameters: Patient Global Assessment (PtGA), Physician's Global Assessment of Disease Activity (PhGA), physical function (using HAQ-DI), visual analog pain scale, and acute phase reactant (using ESR or CRP). ACR 20/50/70 response is achieved if > 20%/> 50%/> 70% improvement in tender joint count (TJC) or swollen joint count (SJC) as well as a > 20%/> 50%/> 70% improvement in > 3 of the other 5 parameters.

[777] Change in Modified Psoriatic Arthritis Response Criteria (PsARC) score: Response is defined by improvement in at least 2 of the 4 following measures, one of which must be joint swelling or tenderness, and no worsening in any of the 4 measures: PtGA (patient global assessment) of articular disease (1-5) and PhGA (physician global assessment) of articular disease (1-5): improvement = decrease by at least one point on the 5 point scale, worsening = increase by at least one point on the 5 point scale. Joint pain/tenderness score and joint swelling score: improvement= decrease by 30%, worsening = increase by 30%. [778] Dactylitis severity score: Changes from baseline in Dactylitis Severity Score at 4, 8, 12, and/or 16 weeks. Each digit with dactylitis is evaluated in a severity scale from 0 to 3 (0 = no dactylitis; 1 = mild dactylitis, 2 = moderate dactylitis, 3 = severe dactylitis). The total score is calculated as the sum of the individual digits dactylitis scores, ranging from a minimum 0 to a maximum of 60, with higher scores corresponding to worse severities.

[779] Clinical Disease Activity Index (CDAI): The Clinical Disease Activity Index (CD Al) is a composite index that is calculated as the sum of the: • 28 tender joint count (TJC), • 28 swollen joint count (SJC), • Patient's Global Assessment of Disease Activity measured on a 10 cm visual analog scale (VAS), where 0 cm = lowest disease activity and 10 cm = highest; • Physician's Global Assessment of Disease Activity -measured on a 10 cm VAS, where 0 cm = lowest disease activity and 10 cm = highest. The CDAI score ranges from 0-76 where lower scores indicate less disease activity. The following thresholds of disease activity have been defined for the CDAI: Remission: < 2.8 Low Disease Activity: > 2.8 and < 10 Moderate Disease Activity: > 10 and < 22 High Disease Activity: > 22.

[780] DAS28: Disease Activity Score (DAS): Changes in DAS28 (utilizing hsCRP) from baseline. The DAS28 is a measure of disease activity in PsA based on Swollen and Tender Joint Counts (out of a total of 28), hsCRP and the Patient's Global Assessment of Disease Activity. A DAS28 score higher than 5.1 indicates high disease activity, a DAS28 score of 3.2 to 5.1 indicates moderate disease activity, a DAS28 score of 2.6 to 3.2 indicates low disease activity, and a DAS28 score less than 2.6 indicates clinical remission.

[781] Maastricht Ankylosing Spondylitis Enthesis Score (MASES): The Maastricht Ankylosing Spondylitis Enthesitis Score quantitates inflammation of the entheses (enthesitis) by assessing pain at the following entheses (sites where tendons or ligaments insert into the bone): 1st costochondral joints left/right; 7th costochondral joints left/right; posterior superior iliac spine left/right; anterior superior iliac spine left/right; iliac crest left/right; 5th lumbar spinous process; and the proximal insertion of the Archilles tendon left/right. The MASES, ranging from 0 to 13, is the number of painful entheses out of 13 entheses. See also L Heuft-Dorenbosch et al., Ann. Rheum. Dis. 62: 127-132 (2003).

[782] The effects of Prevotella histicola Strain B on psoriatic arthritis can be evaluated by one or more of the following criteria:

Tender and Swollen Joint Assessment, Psoriasis Area and Severity Index (PASI), Nail Psoriasis Severity Index (NAPSI), Modified Nail Psoriasis Severity Index (mNAPSI), Mander/Newcastle Enthesitis Index (MEI), Leeds Enthesitis Index (LEI), Spondyloarthritis Research Consortium of Canada (SPARCC), Maastricht Ankylosing Spondylitis Enthesis Score (MASES), Leeds Dactylitis Index (LDI), Patient Global for Psoriatic Arthritis, Dermatology Life Quality Index (DLQI), Psoriatic Arthritis Quality of Life (PsAQOL), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), Psoriatic Arthritis Response Criteria (PsARC), Psoriatic Arthritis Joint Activity Index (PsAJAI), Disease Activity in Psoriatic Arthritis (DAPSA), and Composite Psoriatic Disease Activity Index (CPDAI). See Mease, Arthritis Care & Research 63:S64-S85 (2011).

See also Gladman et al., J Rheumatology 34: 1159-1166 (2007).

Example 5: Capsules Comprising Prevotella histicola

[783] Capsules according to the following recipe in Table i were prepared:

Table i: Prevotella histicola Capsule Composition

^b Adjusted based on the potency of drug substance to ensure targeted strength.

The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329). The capsule was banded with an HPMC- based banding solution. The banded capsule was enteric coated with a poly(methacrylic acid-co-ethyl acrylate) copolymer. Example 6: Capsule Comprising Prevotella histicola

[784] Capsules according to the following recipe in Table ii were prepared:

Table ii: Prevotella histicola Capsule Composition

a Swedish orange Vcap capsules

[785] The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).

[786] The capsule was banded with an HPMC -based banding solution.

[787] The banded capsule was enteric coated with Eudragit L30-D55, a poly(methacrylic acid-co-ethyl acrylate) copolymer.

Example 7: Tablet Comprising Prevotella histicola

[788] As another example, the following recipe in Table iii is prepared.

Table iii: Prevotella histicola Tablet Composition

[789] The tablet is prepared as a 17.4mm x 7.1 mm tablet. The tablet is enteric coated. The tablet contains 3.2 x 10¹¹ TCC of Prevotella histicola Strain B (NRRL accession number B 50329). The Prevotella histicola strain referred to above has been deposited as Prevotella histicola Strain B (NRRL accession number B 50329).

Example 8: A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of Prevotella histicola Strain B in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis

Study Objectives:

[790] The primary objective of the study is to show superiority of Prevotella histicola Strain B over placebo in the treatment of atopic dermatitis. The secondary objectives are to further evaluate the efficacy, safety, and tolerability of Prevotella histicola Strain B. Exploratory objectives aim to evaluate the best daily dose and frequency of dosing for Prevotella histicola Strain B in the treatment of atopic dermatitis, the time to onset of clinical response to Prevotella histicola Strain B and the effect of Prevotella histicola Strain B treatment on blood biomarkers.

Primary endpoint:

[791] The Eczema Area and Severity Index (EASI) will be utilized to measure the extent and severity of a participant’s atopic dermatitis. The percentage change in the EASI score from baseline to Week 12 will be utilized to evaluate the efficacy of Prevotella histicola Strain B over placebo.

Secondary endpoints:

[792] The EASI Score will also be utilized to measure other aspects of clinical benefit of Prevotella histicola Strain Bin the treatment of atopic dermatitis. In addition to EASI, the Investigator’s Global Assessment (IGA), the SCORing Atopic Dermatitis (SCORAD), the use of Rescue Medications, the Dermatology Life Quality Index (DLQI), the Peak Pruritus Numerical Rating Scale (PP-NRS), the Sleep Disturbance Numerical Rating Scale (SD- NRS), and the Patient Oriented Eczema Measure (POEM) will be measured throughout the study.

[793] The severity and frequency of Adverse Events will be used to evaluate the safety and tolerability of Prevotella histicola Strain B.

Exploratory endpoints:

[794] A number of exploratory endpoints will be evaluated to determine further aspects of treatment efficacy including time to achieve clinical response and patient reported health outcomes. Changes in eosinophils, immune protein markers, and immune cell RNA profile will be used to evaluate the effect of Prevotella histicola Strain B treatment on biomarkers in blood. A fecal sample will be used for microbiome profiling. Human Leukocyte Antigen (HLA) typing will be performed in those participants who consent to assess the correlation with clinical outcomes.

Brief Study Design:

[795] This study will evaluate Prevotella histicola Strain B in participants with mild, moderate, and severe atopic dermatitis to compare efficacy, safety, and tolerability to placebo. The Investigational Medicinal Product (IMP) is Prevotella histicola Strain B (drug product thereof) or matching placebo. The study will be blinded to the participants, Investigator, and Sponsor.

[796] Approximately 264 participants will be randomized in a 3 : 1 ratio (198 to Prevotella histicola Strain B: 66 to placebo) and treated for 12 weeks. Following end-of-treatment assessments, participants may enter a 4-week post-treatment follow-up period or may elect to participate in an Open Label Extension (OLE) Protocol for Prevotella histicola Strain B, if available.

[797] Participants will be dosed with Prevotella histicola Strain B or matching placebo administered as the following:

’ Cohort 1: 3.2xlO^u total cells of Prevotella histicola Strain B or matching placebo administered as 1 capsule once daily.

’ Cohort 2: 6.4xlO^u total cells of Prevotella histicola Strain B or matching placebo administered as 2 capsules once daily.

’ Cohort 3: 6.4xlO^u total cells of Prevotella histicola Strain B or matching placebo administered as 1 capsule of 3.2xlOⁿ cells twice daily.

[798] An interim safety and efficacy analysis may be performed after approximately 50% of participants have completed at least 8 weeks of treatment.

[799] Study Duration: The maximum study duration is up to 20 weeks for all participants. Following informed consent, participants will have up to a 4-week screening period, followed by a 12-week treatment period and a post treatment follow-up visit 4 weeks later. Should a participant elect to participate in the OLE protocol, their study duration during this study would be a maximum of 16 weeks.

1. STUDY OBJECTIVE(S)

1.1. Primary Objectives

[800] The primary comparison of interest is the mean difference between Prevotella histicola Strain B and placebo in the percentage change from baseline in EASI score at Week 12. The primary trial objective is to show superiority of Prevotella histicola Strain B over placebo.

[801] The primary comparison will be made while on treatment but without regard to treatment compliance or any changes in background or rescue therapy.

1.2. Secondary Objectives

[802] The secondary objectives of this study are the following:

1. To evaluate the clinical benefit of Prevotella histicola Strain B in the treatment of atopic dermatitis.

2. To evaluate the safety and tolerability of Prevotella histicola Strain B.

1.3. Exploratory Objectives

[803] The exploratory objectives of this study are the following:

1. To evaluate the time to onset of clinical response to Prevotella histicola Strain B.

2. To evaluate the most effective dose and dosing frequency of Prevotella histicola Strain B in the treatment of atopic dermatitis.

3. To evaluate the effect of Prevotella histicola Strain B on patient reported outcomes.

4. To evaluate the relationship of Prevotella histicola Strain B treatment with biomarkers such as immune protein markers, eosinophils, and immune cell RNA profile in blood.

5. To evaluate correlation of genetic markers and Prevotella histicola Strain B treatment outcomes.

6. To evaluate correlation of gut microbiome and Prevotella histicola Strain B treatment outcomes. 2. STUDY VARIABLES

2.1. Efficacy Variable(s)

2.1.1. Primary Efficacy Variable(s)

[804] The primary efficacy endpoint of the study is the effect of Prevotella histicola Strain B on the percent change in the Eczema Area and Severity Index (EASI) score from baseline to Week 12.

2.1.2. Secondary Efficacy Variable(s)

[805] The following secondary endpoints will be evaluated at Weeks 4, 8, 12 and 16 (unless otherwise specified) to evaluate the maximum clinical benefit of Prevotella histicola Strain B in the treatment of atopic dermatitis:

• Mean absolute change and percentage change from baseline in EASI Score

• Percentage of Participants Achieving EASI-50

• Percentage of Participants Achieving EASI-75

• Percentage of Participants Achieving EASI-90

• Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a >2 Point Improvement from baseline

• Percentage of Participants Achieving IGA of 0 or 1

• Percentage of Participants Achieving IGA of 0 [Time Frame: Week 12 and 16]

• Mean absolute change and percentage change from baseline in IGA*BSA

• Mean absolute change and percentage change from baseline in BSA

• Percentage of Participants Achieving B SA-50

• Percentage of Participants Achieving B SA-75

• Percentage of Participants Achieving BSA reduction to 3% BSA or less

• Mean absolute change and percentage change from baseline in SCORing Atopic Dermatitis (SCORAD)

• Percentage of Participants Achieving SCORAD-50

• Percentage of Participants Achieving SCORAD-75

• Mean absolute change and percentage change from baseline in DLQI

• Percentage of Participants achieving a reduction of >4 in the DLQI, of those with a score of >4 at baseline [Time Frame: Week 12 and 16]

• Mean absolute change from baseline in worst Pruritus-NRS

• Percentage of Participants achieving a reduction of >2 in the worst Pruritus-NRS, of those with a score of >2 at baseline • Percentage of Participants achieving a reduction of >4 in the worst Pruritus-NRS, of those with a score of >4 at baseline [Time Frame: Week 12 and 16]

• Mean absolute change from baseline in SD-NRS score

• Percentage of Participants achieving a reduction of >2 in SD-NRS score, of those with a score of >2 at baseline

• Mean absolute change and percentage change from baseline in Patient Oriented Eczema Measure (POEM)

• Percentage of Participants achieving a reduction of >4 in the POEM score, of those with a score of >4 at baseline

• Number of courses of rescue therapy per Participant

• Number of days of treatment with rescue therapy per Participant

• Proportion of participants not requiring rescue therapy

2.2. Pharmacokinetic and Pharmacodynamic Variable(s)

[806] Prevotella histicola Strain B has no systemic absorption and therefore no systemic exposure. Therefore, no samples for pharmacokinetic analysis will be performed in this study.

2.3. Safety Variables

[807] The severity and frequency of adverse events will be used to evaluate the safety and tolerability of Prevotella histicola Strain B. Vitals signs, weight, physical examinations, clinical laboratory tests, ECG and use of concomitant medications will also be used to evaluate the safety and tolerability of Prevotella histicola Strain B.

2.4. Exploratory Variables

[808] The following endpoints will be used to evaluate the time to onset of clinical response to Prevotella histicola Strain B :

• Time to first achievement of EASI-50

• Time to first achievement of IGA of 0 or 1 with a 2-point improvement from baseline

• Time to first achievement of a >2 point in improvement in PP-NRS score, in participants with a score of >2 at baseline

• Time to first achievement of a >4 point in improvement in PP-NRS score, in participants with a score of >4 at baseline

• Time to first achievement of a >2 point in improvement in SD-NRS score, in participants with a score of >2 at baseline [809] The following endpoints will be used to evaluate other aspects of the efficacy of Prevotella histicola Strain B as a treatment for atopic dermatitis at Weeks 4, 12 and 16 unless otherwise specified:

• Percentage of Participants Achieving Investigator's Global Assessment (IGA) of 0 or 1 with a >2 Point Improvement from screening

• Mean absolute change and percentage change from Screening in EASI Score

• Percentage of Participants developing skin infections requiring topical or systemic antibiotic treatment [Time Frame: Week 12]

• Changes from baseline in SF-12 MCS and PCS scores

• Changes from baseline in HADS anxiety and depression scores

• Changes from baseline in ADCT scores

• Daily changes from baseline in the PP-NRS and SD-NRS [Timescale: Days 2 to 112]

[810] The following endpoints will be used to evaluate the effect of Prevotella histicola Strain B treatment on biomarkers in blood at Weeks 2, 12 and 16 (unless otherwise specified):

• Changes from baseline in eosinophils

• Changes from baseline in serum immune protein markers including IgE [Time Frame: Week 12]

• Changes from baseline in immune cell RNA profile

STUDY DESIGN

2.5. Study Description

[811] This is a randomized, double-blind, placebo-controlled study to evaluate the efficacy, safety and tolerability of Prevotella histicola Strain B as compared to placebo in participants with mild, moderate and severe atopic dermatitis.

[812] This study will consist of 3 parallel run cohorts with a possible interim analysis after approximately 50% of participants have completed at least 8 weeks of treatment.

[813] Approximately 264 participants will be randomly allocated (1: 1 : 1 ratio) to the 3 cohorts. Within each cohort, participants will then be randomized to treatment in a 3 : 1 ratio (66 to Prevotella histicola Strain B, 22 to placebo). Therefore, across the three cohorts, approximately 198 participants will be randomly assigned to receive Prevotella histicola Strain B and 66 participants will be randomized to matching placebo for 12 weeks. Following end-of-treatment assessments, participants may enter a 4-week post-treatment follow-up period or may elect to participate in an Open Label Extension (OLE) protocol for Prevotella histicola Strain B, if available.

• Cohort 1: 3.2 x 10¹¹ total cells of Prevotella histicola Strain B or matching placebo administered as 1 capsule once daily.

• Cohort 2: 6.4 x 10¹¹ total cells of Prevotella histicola Strain B or matching placebo administered as 2 capsules once daily.

• Cohort 3: 6.4 x 10¹¹ total cells of Prevotella histicola Strain B or matching placebo administered as 1 capsule of 3.2 x 10¹¹ cells twice daily.

2.6. Study Duration per Participant

[814] All cohorts will consist of:

• Up to a 4-week Screening Period

• A 12-week Treatment Period

• A 4-week Post-Treatment Follow-up Period

[815] Total participant duration is up a maximum of 20 weeks from screening to safety follow-up, unless they elect to participate in the OLE protocol, and their maximum participation in this study would be 16 weeks.

[816] The end of the study is defined as the date of the last visit of the last participant (LPLV).

2.7. Investigational Medicinal Product(s)

[817] All IMP in this study will be administered orally. Prevotella histicola Strain B will be supplied as capsules that are enteric-coated to release the contents upon gastric emptying. The enteric-coated capsules contain lyophilized Prevotella histicola Strain B, mannitol, magnesium stearate, colloidal silicon dioxide, hydroxypropyl methylcellulose, methacrylic acid-ethyl acrylate copolymer, talc, triethyl citrate, titanium dioxide, and iron oxide.

2.8. Investigational Medicinal Product(s) to be Administered

[818] The study IMP (Prevotella histicola Strain B or placebo) will be administered as capsules for 12 weeks in total.

[819] Study IMP is to be taken with water at approximately the same times each day (±2 hours, whenever possible). With twice daily dosing, administration should be in the morning and evening, with the doses separated by approximately 12 hours (±2 hours, whenever possible).

Open Label Extension Option

[820] Participants who complete the 12 weeks of double-blind treatment may have the option to enter an Open Label Extension (OLE) protocol at the Week 12 Visit, if available.

[821] Participants who do not enroll into the OLE will enter a 4-week follow-up period and complete the Week 16 Visit.

Example 9: A Phase 2, Multicenter, Double-Blind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of Prevotella histicola Strain B in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis

[822] A phase 2 clinical is performed as described in Example 8, with the following modifications:

[823] This trial is a 16-week, multi-center, double-blind, placebo-controlled Phase 2 trial for the treatment of mild, moderate, and severe atopic dermatitis. Approximately 300 patients will be randomized into one of three cohorts - each cohort has -100 patients randomized in a 3 : 1 ratio (75 to Prevotella histicola Strain B and 25 to placebo). Cohort 1 will be administered a dose of 1.6 x 10¹¹ total cells of Prevotella histicola Strain B, or matching placebo administered as two capsules once daily. Cohorts 2 & 3 will be administered a dose of 6.4 x 10¹¹ total cells of Prevotella histicola Strain B, or matching placebo administered as two capsules once daily (cohort 2) or one capsule twice daily (cohort 3), respectively. Patients will be dosed for 16 weeks. [824] Cohort 4 will be administered a dose of 8 x IO¹⁰ total cells of Prevotella histicola Strain B or matching placebo administered as one capsule. Patients will be dosed for 16 weeks.

[825] The primary endpoint is percentage of patients achieving an EASI-50 at week 16. Key physician-reported secondary endpoints are IGA (Investigator Global Assessment) and BSA (Body Surface Area). Key patient-reported secondary endpoints are DLQI (Dermatology Life Quality Index), POEM (Patient-Oriented Eczema Measure), and Pruritus-NRS (Numerical Rating Scale).

Example 10: A Long-Term Extension Trial in Participants with Atopic Dermatitis who Participated in Previous Phase 2 And 3 Prevotella histicola Strain B Trials

PROTOCOL SUMMARY

Study Objectives:

[826] The primary objective of the study is to:

• Evaluate the long-term safety and tolerability of Prevotella histicola Strain B in the treatment of atopic dermatitis.

[827] The secondary objective of the study is to:

• Evaluate the efficacy of long-term treatment with Prevotella histicola Strain B in the treatment of atopic dermatitis.

[828] Primary endpoint: The incidence and rate per 100 patient-years of treatment emergent adverse events (TEAEs) during the 36-week treatment and 4-week follow-up period.

[829] Secondary endpoints: The Eczema Area and Severity Index (EASI) Score will be utilized to measure the efficacy of Prevotella histicola Strain B in the treatment of atopic dermatitis. In addition to EASI, the Investigator’s Global Assessment (IGA), percentage of Body Surface Area (BSA), Product of the IGA and BSA (IGA*BSA), the SCORing Atopic Dermatitis (SCORAD), the Dermatology Life Quality Index (DLQI), the Peak Pruritus Numerical Rating Scale (PP-NRS), the Sleep Disturbance Numerical Rating Scale (SD- NRS), the Patient Oriented Eczema Measure (POEM) and the Atopic Dermatitis Control Tool (ADCT) will be measured throughout the study.

[830] The number of courses of treatment with rescue therapies and with antibiotic treatment due to skin infection, per participant, will also be measured. [831] Brief Study Design: This is an Open-Label Extension (OLE) study to evaluate the long-term safety, tolerability, and efficacy of Prevotella histicola Strain B in participants with mild, moderate, and severe atopic dermatitis who have completed the treatment period of a prior clinical study (“parent study”) with Prevotella histicola Strain B. The parent study of this open label extension protocol is described in Example 9: A Phase 2, Multicenter, DoubleBlind, Placebo-Controlled, Multiple-Cohort Study Investigating the Effect of Prevotella histicola Strain B in Participants for the Treatment of Mild, Moderate and Severe Atopic Dermatitis. This study will be referenced as the parent study throughout the protocol.

[832] This study may serve as an open label extension study for future Prevotella histicola Strain B studies in Atopic Dermatitis.

[833] All participants in this study will be treated with Prevotella histicola Strain B, regardless of the treatment assignment in the parent study. To minimize bias, during dosing in this OLE, investigators and participants will continue to be blinded to participants’ treatment allocation in the parent study whilst it is ongoing. Participants in this study will be treated with Prevotella histicola Strain B for up to 36 weeks, followed by a follow-up visit at approximately 4 weeks after the end of treatment.

[834] Interim safety and efficacy analyses may be performed throughout the study as required for ongoing evaluation of the benefit-risk profile for Prevotella histicola Strain B. These may include either all participants enrolled in the study or use of a subset of participants who transitioned to this study from a specific parent study. Interim analyses may also incorporate data collected within the parent studies that feed into this study.

[835] Study Duration: The maximum study duration is up to 40 weeks for all participants, which will include a 36-week treatment period and a 4-week post treatment follow-up period. The participants may move directly from the parent study into the open label treatment phase without a break in study treatment, or within 7 days of completing the treatment period of the parent study. If the participants move directly into this study without a break in treatment from the parent study, the Day -1 visit should be performed at the same time as the end of treatment visit of the parent study.

2. INTRODUCTION

2.9. Atopic Dermatitis

[836] Atopic dermatitis (AD), also known as (atopic) eczema, is a chronic, highly symptomatic relapsing inflammatory skin disease, affecting up to 30% of children and 10% of adults (Bieber, Atopic Dermatitis, 2010). While AD often begins in infancy or childhood, it may become chronic and persist into adulthood (Katoh, 2019). Depending on factors such as severity of skin lesions or body surface area coverage, the disease can be classified clinically as mild, moderate, or severe.

[837] Patients with AD typically have highly symptomatic skin lesions that may present acutely with erythema, exudates, papulovesicles, scales and crusts, often symmetrically distributed on the body (Katoh, 2019). The disease typically follows a variable course with acute flares, often triggered by external factors, which cause a worsening of skin disease and symptoms. More chronic lesions are associated with thickened lichenified skin which may be accompanied by pigmentary changes and further excoriations (Bieber, Atopic Dermatitis, 2010). The primary symptom at both stages of disease is typically pruritus (itch). Such signs and symptoms are associated with a substantial patient burden that typically includes sleep disturbance, mood disturbance, mental health problems (Simpson, 2012), and poor quality of life and social functioning (Kiebert, 2002).

[838] AD, like other atopic diseases, is characterized by a T helper type 2 (Th2) cell- mediated inflammation, with upregulation of Th2 cytokines including IL-4, IL-5, and IL- 13 (Indra, 2013). In turn, this leads to increased IgE production by B cells, which can trigger release of cytokines and chemical mediators such as histamine from mast cells and Langerhans cells. In addition, thymic stromal lymphoprotein is thought to be a critical cytokine in the triggering and maintenance of AD (Indra, 2013) and is associated with migration of Th2 cells into the skin lesion (Katoh, 2019). The resulting systemic inflammation drives the disease pathology and patient symptoms, with the resultant scratching of pruritic lesions further worsening the skin lesions and the skin barrier function, further driving the disease process. Therefore, targeting systemic inflammation improves disease signs and symptoms - for example, systemic corticosteroids typically lead to rapid clinical improvements, but generally are not acceptable as a long-term treatment due to associated side-effects (Lee, 2016).

[839] In general, treatment of AD is aimed at a combination of resolution of skin disease and improvement of symptoms, such as itch (acute therapy), and also prevention of further flares (maintenance therapy). Emollients, also known as moisturizers, are the first-line and baseline therapy for all severities of disease, and act by treating the defective skin barrier and providing cutaneous hydration (Lee, 2016). There are a number of other topical treatments including topical corticosteroids (TCS) and topical calcineurin inhibitors (TCI) (Katoh, 2019). Newer topical therapies for AD include Janus Kinase (JAK) and Phosphodiesterase 4 (PDE) inhibitors (Bieber, 2021). Unfortunately, there are associated issues with such current treatments including adverse effects, limitations in efficacy, and low patient acceptability and tolerability, particularly when used as chronic treatment options.

[840] There are currently no licensed oral treatments for mild to moderate atopic dermatitis. There are currently two classes of oral medications approved for the treatment of moderate to severe atopic dermatitis: Ciclosporin (approved in the European Union (EU)) and JAK inhibitors (newly approved in the EU and US). Due to its associated risks and side-effects, such as renal failure, ciclosporin is generally only recommended for short-term use (Katoh, 2019). The most common serious adverse reactions associated with JAK inhibitors are infections; others include nausea, headache, and acne. Other antiinflammatory treatments, such as methotrexate or azathioprine are, therefore, used off- license in order to reduce the Th2-driven systemic inflammation. These systemic treatments all have associated risks and side-effects and are, therefore, not suitable for a large population of patients, including many of those with mild and moderate disease. Finally, for patients with moderate-to-severe disease, dupilumab and tralokinumab are now licensed as a biologic injectable treatment and are currently used to treat a small proportion of patients with such disease severity.

[841] A 2016 patient survey (National Eczema Association, 2016) highlights and summarizes what it is like for patient living with atopic dermatitis:

• 84% are “very” or “extremely” bothered by dry skin, 83% by itch, and 63% by rash/redness

• 75% stated AD interferes with their job and house chores, 71% say it interferes with hobbies, and 65% don’t feel as healthy because of AD

• Nearly half of people with moderate to severe AD report their disease “interferes with their social life, intimate relations, and relationships with their spouse and children”

• 1 in 3 takes one or more hours per day to treat their AD

• More than half are dissatisfied overall with each of the following treatments that they are using or have used: topical steroids, topical calcineurin inhibitors, phototherapy, and oral medications

[842] The conclusion from this study was that there is a “lack of safe and effective treatments” for AD, allowing for “unchecked symptoms [which] contribute to the range of health issues.” This sums up the unmet need for and importance of further oral treatments for AD.

2.10. Previous Experience with Prevotella histicola Strain B and Rationale for Treating Atopic Dermatitis

[843] The small intestinal axis (SINT AX™) is the network of anatomical and functional connections that has evolved to link the small intestine and the rest of the body. It links small intestinal mucosal immunology with systemic inflammation and is accessible with oral SINT AX medicines.

[844] The inflammatory control mechanisms of SINT AX down-regulate multiple inflammatory pathways including those that have been validated with targeted antibody therapies, but without the side effects seen with antibody therapeutics or broadly acting oral kinase inhibitors. This occurs via specific interactions between the oral SINTAX therapy and small intestine enterocytes and immune cells. These interactions drive the development of an immune-regulatory subset of lymphocytes that travel from the gut to the systemic circulation, via the mesenteric lymph nodes. Here, these circulating cells mediate their effects on peripheral inflammation at the target sites (e.g., atopic dermatitis skin).

[845] Prevotella histicola Strain B is a pharmaceutical preparation of a single strain of Prevotella histicola, originally isolated from a duodenal biopsy. The drug substance is essentially non-viable and non-replicating, with a cell viability of < 0.02%. It has not been genetically modified. It does not colonize the gut nor alter the microbiome and has no detectable systemic exposure following oral dosing to date - i.e., it is gut-restricted.

[846] Prevotella as a genus are gram-negative, obligate anaerobic bacteria that are natural human commensals found in the oral cavity and gastrointestinal (GI) tract. Strains of Prevotella have been found in all human populations tested to date, at abundances ranging from < 1% to nearly 50% of total fecal microbial load (Vandeputte, Kathagen, & D'hoe, 2017).

[847] In vitro studies of Prevotella histicola Strain B in human and mouse cellular assays and in vivo models support its use in the treatment of immunoinflammatory diseases, including atopic dermatitis. Oral administration of Prevotella histicola Strain B to mice led to striking therapeutic effects on delayed-type hypersensitivity (DTH), imiquimod-induced skin inflammation, fluorescein isothiocyanate (FITC) cutaneous hypersensitivity, collagen- induced arthritis (CIA) (Marietta, Murray, & Luckey, 2016) and experimental acute encephalomyelitis (EAE) (Mangalam, Shahi, & Luckey, 017) in in vivo models. Prevotella histicola Strain B was shown to down-regulate key Th2 -related cytokines including IL-4 and IL-31. No potentially related adverse effects were seen in the animals used in these experiments with daily dosing for up to 3 weeks, or alternate day dosing for over 7 weeks. Ex vivo immunophenotyping in these models shows increased regulatory T cell numbers and regulatory dendritic cells (DCs) in spleen and mesenteric lymph nodes, as well as decreases in pro-inflammatory cytokines such as IL-23 p40, IL- 17, and IL-13. Prevotella histicola Strain B does not suppress the expression of Type-1 interferons in these ex vivo experiments, suggesting that the broad spectrum of anti-inflammatory effects is achieved without damaging mechanisms of immune surveillance critical for avoiding cancers and pathogens. Treatment also led to enhancement of gut intestinal barrier integrity, which is often disrupted in patients with inflammatory diseases. The effects on immune parameters have been observed both within and outside of the GI tract, which demonstrates that hostmicrobe interactions in the gut can affect the immune response in peripheral tissues.

[848] This pre-clinical data therefore supported advancing Prevotella histicola Strain B into the treatment of atopic dermatitis, due to the resolution of systemic inflammation including in models of Th2-driven disease and the reduction of Th2-dervied cytokines that are known to drive the pathophysiology of atopic dermatitis.

[849] Clinical data is accumulating that supports both the role of the small intestinal axis in humans and that it can be harnessed by Prevotella histicola Strain B as a potent modulator of systemic inflammation, and in Thl-, Th2-, and Thl7-mediated inflammation. As of January 2022, a total of 458 adult participants have been exposed to Prevotella histicola Strain B in the phase 1 and 2 studies. To date, Prevotella histicola Strain B is well tolerated with a safety profile comparable to placebo, and there are no AEs of special interest.

[850] In the Phase lb study, 16 participants with mild or moderate atopic dermatitis in cohort 7 were treated with Prevotella histicola Strain B capsules at a dose of 8.0 x 10¹¹ cells once daily for 8 weeks, with a further 8 participants given matching placebo. Clinically meaningful and significant responses were observed at the end of the treatment period, in terms of the changes in EASI, IGA*BSA and SCORAD, as well as within the patient- reported outcomes, which also found improvements in itch and sleep scores. A further 16 participants were treated with Prevotella histicola Strain B daily for 8 weeks at a capsule dose of 6.4 x 10¹¹ total cells, with another 8 participants on placebo in cohort 10 of this study. In this cohort, Prevotella histicola Strain B was shown to be well-tolerated with no treatment-related adverse events of moderate or severe intensity and no serious adverse events through eight weeks of dosing. The above efficacy was not clearly replicated in this small cohort, although the primary endpoint of safety and tolerability was. The safety profile was consistent with that seen in other studies of Prevotella histicola Strain B.

[851] The available evidence to date has found Prevotella histicola Strain B to be well tolerated with evidence for proof of concept as a potential effective treatment for atopic dermatitis. A well tolerated oral therapy could offer significant benefit in atopic dermatitis for all severities of disease.

3. STUDY OBJECTIVE(S)

3.11. Primary Objectives

[852] The primary study objective is to evaluate the long-term safety and tolerability of Prevotella histicola Strain B in the treatment of atopic dermatitis. The primary endpoints to measure this objective will be the incidence and rate per 100 patient-years of treatment- emergent adverse events during the 36-week treatment period and the 4-week follow-up period of this study, and during the treatment period of this study and the relevant parent study.

[853] TEAEs will be defined as all events starting after first dose of study drug and on or before 28 days after last dose for each participant. All TEAEs will be included in the assessments of incidences and rates, regardless of compliance with study medication, use of other medications, or deviations from the study protocol.

3.12. Secondary Objectives

[854] The secondary objective of this study is to evaluate the efficacy of long-term treatment with Prevotella histicola Strain B in the treatment of atopic dermatitis.

3.13. Exploratory Objectives

[855] The exploratory objectives of this study are the following:

2. To evaluate other aspects of the efficacy of Prevotella histicola Strain B as a treatment for atopic dermatitis.

3. To evaluate the relationship of Prevotella histicola Strain B treatment with biomarkers such as immune protein markers and immune cell RNA profile in blood. 4. STUDY VARIABLES

4.14. Safety Variable(s)

4.14.3. Primary Safety Variable(s)

[856] The primary safety variables will be the incidence and rate per 100 patient-years of TEAEs. Both the period defined by this study alone and the period defined by this study and the relevant parent study will be reported.

[857] Subgroups of TEAEs will be evaluated as follows:

• All TEAEs

• TEAEs of Grade 2 or above

• TEAEs of Grade 3 or above

• Serious TEAEs

• Fatal TEAEs

• TEAEs causing discontinuation of study drug

• Study drug related TEAEs Study (defined by an investigator assessment of possible, probable, or definite relationship to IMP)

• Study drug related TEAEs of Grade 2 or above

• Study drug related TEAEs of Grade 3 or above

• Study drug related serious TEAEs

• Study drug related fatal TEAEs

• Study drug related TEAEs causing discontinuation of study drug

4.14.4. Secondary Efficacy Variable(s)

[858] The following secondary endpoints will be evaluated at all scheduled visits to evaluate the maximum efficacy of Prevotella histicola Strain B in the treatment of atopic dermatitis. For all measures involving changes from baseline, the baseline assessment from the relevant Prevotella histicola Strain B parent study will be used.

• Percentage of participants achieving EASI-50

• Percentage of participants achieving EASI-75

• Percentage of participants achieving EASI-90

• Mean absolute change and percentage change from baseline in EASI Score

• Percentage of participants achieving IGA of 0 or 1 with a > 2 point improvement from baseline

• Percentage of participants achieving IGA of 0 or 1

• Percentage of participants achieving IGA of 0 • Mean absolute change and percentage change from baseline in IGA*BSA

• Mean absolute change and percentage change from baseline in BSA

• Percentage of participants achieving BSA-50

• Percentage of participants achieving B SA-75

• Percentage of participants achieving BSA reduction to 3% or less

• Mean absolute change and percentage change from baseline in SCORAD

• Percentage of participants achieving SCORAD-50

• Percentage of participants achieving SCORAD-75

• Mean absolute change and percentage change from baseline in DLQI

• Percentage of participants achieving a reduction of > 4 in the DLQI, of those with a score of > 4 at baseline

• Mean absolute change from baseline in PP-NRS

• Percentage of participants achieving a reduction of > 2 in the PP-NRS, of those with a score of > 2 at baseline

• Percentage of participants achieving a reduction of > 4 in the PP-NRS, of those with a score of > 4 at baseline

• Mean absolute change from baseline in SD-NRS

• Percentage of participants achieving a reduction of >2 in the SD NRS, of those with a score of > 2 at baseline

• Percentage of participants achieving a reduction of > 4 in the POEM score, of those with a score of > 4 at baseline

• Number of courses per patient-year of any rescue medication (not including antibacterial therapy)

• Number of courses per patient-year of topical corticosteroids of any potency

• Number of courses per patient-year of topical tacrolimus (0.1%), topical pimecrolimus (1%) or grade VII topical corticosteroid

• Number of courses per patient year of moderate potency (grade IV and V) topical steroids

4.14.5. Exploratory Variables

[859] The following endpoints will be used to evaluate the time to onset of clinical responseo Prevotella histicola Strain B: • Time to first achievement of EASI-50

• Time to first achievement of sustained EASI-50 (sustained EASI-50 response is defined as one which is present at consecutive visits spanning at least 8 weeks in the absence of rescue medication)

[860] The following endpoints will be used to evaluate other aspects of the efficacy of Prevotella histicola Strain B as a treatment for atopic dermatitis:

• Changes from baseline in ADCT scores

• Mean absolute and percentage change in the four body region scores of the EASI

• Percentage of participants achieving at least a 50% reduction in each of the four body region scores of those with a non-zero score for the relevant region at baseline

• Percentage of participants who change response states from Day -1 to Weeks 8, 16, 24 and 36. Response states will be defined using the EASI score percentage change from baseline with categories for > 25% increase, no change (< 25% increase to < 25% decrease), 25% to < 50% decrease, 50% to < 75% decrease, 75% to < 90% decrease, > 90% decrease).

• Daily mean absolute change from baseline in PP-NRS and SD-NRS scores.

[861] The following endpoints will be used to evaluate the relationship of Prevotella histicola Strain B treatment with biomarkers such as immune protein markers and immune cell RNA profile in blood.

• Changes from baseline in serum immune protein markers including IgE

• Changes from baseline in immune cell RNA profile

4.15. Pharmacokinetic and Pharmacodynamic Variable(s)

[862] The following endpoints will be used to evaluate the relationship of Prevotella histicola Strain B treatment with biomarkers such as immune protein markers and immune cell RNA profile in blood. Prevotella histicola Strain B has no systemic absorption and therefore no systemic exposure. No samples for pharmacokinetic analysis will be performed in this study.

4.16. Safety Variables

[863] The severity and frequency of adverse events will be used to evaluate the safety and tolerability of Prevotella histicola Strain B. Vitals signs, weight, physical examinations, clinical laboratory tests, ECG and use of concomitant medications will also be used to evaluate the safety and tolerability of Prevotella histicola Strain B. 5. STUDY DESIGN

5.17. Study Description

[864] This is an Open-Label Extension, multicenter study to evaluate the long-term safety, tolerability, and efficacy of Prevotella histicola Strain B in participants with mild, moderate, and severe atopic dermatitis. Participants who have completed the 16-week treatment period in the parent study may be eligible to enroll in this study.

5.18. Study Duration per Participant

[865] The total duration of participation in this study is up to a maximum of 40 weeks from Day -1 to follow-up.

[866] Participants will undergo:

• A Day -1 Visit

• A 36-week Treatment Period consisting of 6 study visits

• A 4-week Post-Treatment Follow-up Visit

[867] The end of the study is defined as the date of the last visit of the last participant (LPLV).

5.19. Planned Number of Participants

[868] This study will be conducted as a multi-center study. The total number of participants will be dependent on the number of participants who elect and are eligible to participate in the Open Label Extension study following participation in the parent study.

5.20. Schedule of Study Assessments

Table 5-1: Schedule of Assessments

* Assessments performed at the End of Treatment Visit of the parent study that do not need to be repeated if this visit occurs on the same day as the Initial Visit of the OLE (Day -1).

^a' Informed consent must be obtained by the Principal Investigator or a SubInvestigator per Good Clinical Practice (GCP) and local guidelines. The Informed consent form can be provided to the participant prior to the end of treatment visit in the parent study, however, must be signed on Day -1 of this study. b- Review any changes to smoking and medical history since baseline of parent study. ^c' A physical examination will be conducted at every visit. At Day -1 and Week 36 a full PE will be performed, and the following body systems will be evaluated: general appearance, cardiovascular, respiratory, gastrointestinal, musculoskeletal, central nervous system, lymph nodes and skin. At all other visits, a brief PE will be performed, and the following body systems will be evaluated: general appearance, cardiovascular, respiratory, gastrointestinal, and skin. - BMI will be calculated from the height and weight measurements. ^e' Women of child-bearing potential only. Pregnancy testing (urine) will be performed at the visits indicated and if a menstrual cycle is missed or if pregnancy is otherwise suspected. f

A single ECG tracing is to be obtained on the day of the visit after the participant has rested for 5 minutes in supine position. If, in the opinion of the Investigator, there appears to be clinically significant findings, repeat tracings should be obtained, as necessary. ^g' Results from the laboratory assessments performed at the Day-1 visit will not be required to confirm eligibility for participation in the study. The investigator may use results from the parent study to confirm eligibility.

Blood pressure, heart rate, respiratory rate, and temperature will be measured after the participant has rested for at least 5 minutes in supine position.

^L Study staff will assist the participant in the transition of studies within their eDiary device at the Day-1 visit. The staff will review the eDiary with participants at each visit. eDiaries will be reviewed for completeness and accuracy, and participants will be coached as needed on compliance with the protocol.

^J' Parent study Cohort 3 participants that are confirmed as eligible to participate in this study at the Day-1 visit will be randomized 1 : 1 to receive either 1.6 x 10¹¹ total cells of Prevotella histicola Strain B, or 6.4 x 10¹¹ total cells of Prevotella histicola Strain B. ^k' Study medication will be dispensed after all Day -1 activities are completed and if the participant is confirmed as eligible to participate in the study. The participant will be instructed to take the first IMP dose on Day 1 at home. The capsules are to be taken once daily at approximately the same time each day. On study visit days, dosing may occur at home prior to the study visit. Participants should refrain from consuming acidic drinks 1 hour either side of dosing and from eating 2 hours before dosing and 1 hour after dosing. Participants will be required to record their daily dosing in the eDiary.

^1- AD Investigator rating scales. Participants will be asked to withhold all emollients, sunscreens, or moisturizers on the day of these study visits until all study assessments are completed. m' The Pruritus-NRS (worst itch) and the Sleep Disturbance-NRS (SD-NRS) scale will be asked daily from the Day-1 Visit to the Week 40 or Early Termination Visit (if applicable) via the participant eDiary. n' Digital photographs should be taken of the upper and lower body (upper & lower anterior and upper & lower posterior) as half body shots. Additional close-up photographs of up to six specific body areas (i.e., limbs, trunk and back) may also be taken. The same sites photographed in the parent study should be followed throughout this study for each participant.

°' Participants who withdraw from the study early will have an Early Termination Visit. If due to treatment failure, this visit should be arranged within 72 hours of the start of any new AD therapy, when possible. The participant will also be asked to have a final telephone call 28 days (+3 days) after taking their last dose of IMP for safety assessments. The date of this telephone call will be considered the end of study date for these participants. p' Adverse Events (AE) and Serious Adverse Events (SAE) will be captured from the time the participant signs the informed consent.

5.21. Rationale for study design and selection of dose

5.21.1. Dose Rationale

[869] The doses, and corresponding regimen selected for evaluation within this study are:

• 1.6 x 10¹¹ total cells of Prevotella histicola Strain B administered as 2 capsules once daily.

• 6.4 x 10¹¹ total cells of Prevotella histicola Strain B administered as 2 capsules once daily.

• 8 x IO¹⁰ total cells of Prevotella histicola Strain B administered as 1 capsule once daily.

[870] No placebo will be administered in this study. The following will apply for all participants who transition from the parent study into this study:

• Parent study Cohort 1 participants will receive 1.6 x 10¹¹ total cells of Prevotella histicola Strain B in this study.

• Parent study Cohort 2 participants will receive 6.4 x 10¹¹ total cells of Prevotella histicola Strain B in this study. • Parent study Cohort 3 participants will be randomized 1 : 1 to receive either 1.6 x 10¹¹ total cells of Prevotella histicola Strain B, or 6.4 x 10¹¹ total cells of Prevotella histicola Strain B in this study.

• Parent study Cohort 4 participants will receive 8 x IO¹⁰ total cells of Prevotella histicola Strain B in this study.

[871] The pharmacological site of action of Prevotella histicola Strain B is within the epithelium of the small intestine where Prevotella histicola Strain B interacts with immune and epithelial cells. These interactions modify the systemic immune system and promote inflammation resolution throughout the body. The preclinical and clinical data generated to date suggest this is a broad effect working across Thl, Th2 and Th 17 pathologies. As the intent is to generate a maximal inflammation-resolving phenotype regardless of inflammation pathology, the dose response is expected to be common across indications, and therefore we aim to cross compare to previous studies to support this hypothesis.

[872] A Phase 1 Study evaluated Prevotella histicola Strain B for the treatment of atopic dermatitis with an oral dose of 8.0 x 10¹¹ cells delivered as 10 capsules once a day for 8 weeks. This dose was safe and well tolerated and clinical benefit was observed with an improvement of 50-65% over placebo by Week 8 in EASI and vIGA*BSA endpoints, together with improvements in other measures such as the SCORAD. In addition, 7 out of 16 (44%) participants dosed with Prevotella histicola Strain B for 8 weeks achieved an EASI-50 by day 70, compared with 0% in the placebo group. An additional cohort investigated a dose of 6.4 x 10¹¹ total cells administered daily for 8 weeks. Safety and tolerability were replicated in this cohort.. Efficacy is being further evaluated.

[873] A Phase 2 dose ranging study in psoriasis was conducted in approximately 225 participants for 16 weeks, at doses of 0.8 x 10¹¹, 3.2 x 10¹¹, and 8.0 x 10¹¹ cells.

6. SELECTION AND WITHDRAWAL OF PARTICIPANTS

[874] Participants with a confirmed diagnosis of mild, moderate, or severe atopic dermatitis will be treated in this study only if they meet all inclusion and no exclusion criteria. Any participant who signs the informed consent form will be considered enrolled in the study. Study eligibility procedures will begin after participants sign the informed consent. 6.22. Inclusion criteria

[875] To be eligible to participate in this study, all the following criteria must be met:

1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements.

2. Must have completed the treatment period in a parent study of Prevotella histicola Strain B in the treatment of atopic dermatitis and complied with the protocol to the satisfaction of the investigator.

3. All participants must agree to continue the use of a bland additive-free, sodium lauryl sulfate (SLS)-free, and fragrance-free emollient cream, gel, or ointment at least twice daily (or more, as needed) throughout the study.

4. Continue to meet the following contraception criteria: i. Male participants: i. A male participant must agree to use contraception during their participation in this study and for a period of 90 days after the last dose and refrain from donating sperm during this period. ii. Female participants: i. A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies:

1. Not a woman of childbearing potential (WOCBP) or

2. A WOCBP who continues to follow the contraceptive guidance provided in the parent study during participation in this study, including (if applicable) 7 days prior to the first dose, and for at least 1 complete menstrual cycle (> 30 days) after the last dose.

6.23. Exclusion criteria

[876] Participants are not permitted to participate in this study if any of the following criteria is met:

1. Participants who are currently enrolled in another investigational drug study or plans to receive another investigational agent during this study.

2. Have any other conditions, which, in the opinion of the Investigator or Sponsor, would make the participant unsuitable for inclusion or could interfere with the participant participating in or completing the study. 3. Treatment with phototherapy, a biologic agent, or a systemic immunosuppressive agent that could affect AD, including systemic corticosteroids, within 7 days prior to Day -1, unless used as a rescue treatment as part of the parent study protocol.

4. Treatment with topical atopic dermatitis therapies, including topical corticosteroids, topical calcineurin inhibitors, topical PDE-4 inhibitors, and topical JAK inhibitors, within 7 days prior to Day -1, unless used as a rescue treatment as part of the parent study protocol.

5. Has received live or live-attenuated vaccination within 7 days prior to Day -1 or intends to have such a vaccination during the study. Non-live and non-replicating vaccines are permitted.

6. Hypersensitivity to P histicola or to any of the excipients.

7. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator.

6.24. Screen Failures

[877] Screen failures are defined as participants who consent to participate in the clinical study but are not subsequently entered in the study due to failure to meet eligibility criteria. There is no screening period within this study; however, if the participant fails to meet the eligibility criteria, they will be defined as a screen failure. A minimal set of screen failure information is required to confirm transparent reporting of screen failure participants to meet the Consolidated Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries from regulatory authorities. Minimal information includes informed consent, demography, screen failure details, eligibility criteria, and any AEs and SAEs.

6.25. Discontinuation from Treatment and/or Withdrawal

[878] Participants may discontinue from treatment and withdraw their participation from the study at any time and for any reason without prejudice to their future medical care by the Investigator or at the study site. Every effort should be made to keep participants in the study. The reasons for participants discontinuing treatment and withdrawing from the study will be recorded in the source files and on the eCRF.

[879] Interruption of treatment is defined as a temporary stopping of IMP that resumes during the treatment period, due to an AE or any other reason. The maximum permitted interruption is 14 consecutive days. Participants should have 80% compliance with IMP administration between any two visits after allowing for permitted interruptions. [880] Early discontinuation of treatment is defined as permanent stopping of IMP before the Week 36 visit. Investigators will strive to confirm that a participant who has interrupted treatment for a particular reason will not discontinue IMP unless discontinuation is medically imperative in the Investigator’s judgment. However, a dose interruption of more than 14 consecutive days or multiple dose interruptions resulting in < 80% compliance with IMP administration between any two visits may result in discontinuation of IMP and early termination of the participant.

[881] Early withdrawal from the study is defined as failing to complete the 36- week treatment and the follow-up visit.

[882] A participant will discontinue IMP and be withdrawn from the study for any of the following reasons:

1. The participant experiences treatment failure, demonstrated by the participant commencing phototherapy, an oral agent, biological, or intermediate or high-potency topical therapy for atopic dermatitis, other than those permitted as rescue therapy.

2. The participant has a serious or intolerable AE that in the Investigator’s opinion requires discontinuation from IMP and withdrawal from the study.

NB: Dosing may be interrupted at the Investigator’s discretion due to AE or intercurrent illness for a period of up to 14 consecutive days, following which the participant may resume treatment if the Investigator considers it safe to do so. The participant should discontinue treatment permanently if the same AE which caused dose interruption occurs a second time requiring another dose interruption and is believed to be related to treatment.

3. The participant has symptoms or an intercurrent illness not consistent with the protocol requirements or that justifies withdrawal.

4. The participant is lost to follow-up.

5. Other reasons (e.g., pregnancy, development of contraindications to use of IMP).

6. The participant withdraws consent, or the Investigator or Sponsor decides to discontinue the participant’s participation in the study.

[883] A participant may discontinue IMP and be withdrawn from the study for any of the following reasons:

1. The participant is noncompliant with the protocol.

2. The participant has laboratory safety results that reveal clinically significant hematological or biochemical changes from the baseline values. 3. If the participant is required to start therapy for a concurrent condition that may affect the study endpoints, e.g., a disease modifying agent for asthma.

[884] Investigators should contact the Medical Monitor, whenever possible, to discuss the treatment discontinuation and withdrawal of a participant in advance of this decision.

Investigators should attempt to obtain information on participants in the case of treatment discontinuation and withdrawal. All results of these evaluations and observations, together with a narrative description of the reason(s) for removing the participant, must be recorded in the source documents. The CRF must document the primary reason for treatment discontinuation and withdrawal.

6.25.2. Withdrawal from the Study

[885] Participants may withdraw from the study at any time at their own request or they may be withdrawn at any time at the discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. The Investigator will also withdraw a participant if the Sponsor terminates the study.

[886] If the participant withdraws consent for disclosure of future information, the Sponsor may retain and continue to use any data collected before such a withdrawal of consent.

6.25.3. Lost to Follow-Up

[887] A participant will be considered lost to follow-up if they repeatedly fail to return for scheduled visits and is unable to be contacted by the study site.

[888] The following actions must be taken if a participant fails to return to the study site for a required study visit:

• The site must attempt to contact the participant and reschedule the missed visit as soon as possible and counsel the participant on the importance of maintaining the assigned visit schedule and ascertain whether the participant wishes to and/or should continue in the study.

• Before a participant is deemed lost to follow-up, the investigator or designee must make every effort to regain contact with the participant (where possible, 2 telephone calls and, if necessary, a written message to the participant’s last known mailing address or local equivalent methods). These contact attempts should be documented in the eCRF (date and summary of the phone call and copy of the written message in the source documents). [889] If the participant continues to be unreachable, they will be considered to have withdrawn from the study.

7. STUDY TREATMENT(S)

7.1. Investigational Medicinal Product(s)

[890] Investigational Medicinal Product (IMP) is defined as any investigational treatment(s), marketed product(s), placebo, or medical device(s) intended to be administered to a study participant according to the study protocol.

[891] All participants in this study will be dosed with Prevotella histicola Strain B, administered orally for 36 weeks in total. Prevotella histicola Strain B will be supplied as capsules that are enteric coated to release the contents upon gastric emptying. Prevotella histicola Strain B enteric-coated capsules contain lyophilized Prevotella histicola, mannitol, magnesium stearate, colloidal silicon dioxide, hydroxypropyl methylcellulose, methacrylic acid-ethyl acrylate copolymer, talc, triethyl citrate, titanium dioxide, and iron oxide. The drug substance used for the 1.6xlOⁿ total cells dose (8.OxlO¹⁰ cells/enteric coated capsule), is manufactured by a different process than used for the 6.4xlOⁿ total cells dose (3.2xlOⁿ cells/enteric coated capsule). Drug substances from both processes have been demonstrated to be similar in DTH mouse and healthy-volunteer human models.

7.2. Investigational Medicinal Product(s) to be Administered

[892] The Prevotella histicola Strain B (study IMP) will be administered as capsules for 36 weeks in total.

[893] Study IMP is to be taken with water at approximately the same times each day.

[894] Participants should refrain from consuming acidic drinks (such as cola/soda, coffee, sports and energy drinks, flavored waters, and citrus juices) 1 hour either side of dosing and from eating 2 hours before and 1 hour after dosing.

[895] No placebo will be administered in this study.

Table 7-1: IMP to be Administered

[896] All IMP will be prepared in blister wallets of 10 capsules. Three blister wallets will be packaged in a carton. Cartons will be dispensed per the schedule of assessments (SOA).

7.4. Labeling

[897] Cartons and study wallets will be labelled and released in accordance with International Council for Harmonisation (ICH) Guidelines on Good Clinical Practice (GCP) and Good Manufacturing Practice (GMP) and will include any country required statements. Supplies will be identified by the batch number and expiry date which will be used by the Interactive Response Technology (IRT) system to identify content and allocate cartons to study participants.

7.5. Handling and Storage Requirements

[898] The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. Investigational medicinal product stored by the Investigator is to be kept in a secured area with limited access according to the storage conditions mentioned on the label.

[899] Appropriate storage conditions must be confirmed either by controlling the temperature (e.g., room, refrigeration unit) or by completion of a daily temperature log in accordance with local requirements, showing actual and minimum/maximum temperatures reached over the last 24-hour time period.

[900] The Investigator (or designee) will instruct the participant to store the IMP at home following the instructions on the label.

7.6. IMP Accountability

[901] An Interactive Response Technology (IRT) system will be used to record IMP dispensing and return information on a by-participant basis during the study. Details of any IMP lost, damaged (due to breakage or wastage), not used, partially used, disposed of at the study site, or returned to the Sponsor or designee must also be recorded. All supplies and pharmacy documentation must be made available throughout the study for the Sponsor (or designee) to review. [902] Participants will utilize an electronic diary (eDiary) to record their IMP intake on a daily basis (Section 7.6.4 eDiary).

[903] The Investigator (or designee) is responsible for retaining all used, unused, and partially used containers of IMP until returned or destroyed.

[904] The Investigator may assign some of the Investigator’s duties for IMP accountability at the study site to an appropriate pharmaci st/designee.

[905] The Investigator must verify that the IMP is used only in accordance with the protocol.

[906] All used (including empty containers)/partially used, unused, damaged, and/or expired IMP must be reconciled and returned to the Sponsor or designee, or it may be destroyed at the site according to applicable laws and regulations, and Sponsor SOPs, if applicable. Investigational medicinal product intended for the study cannot be used for any other purpose than that described in this protocol.

7.6.4. eDiary

[907] The primary purpose of the diary is to enhance participant compliance with the protocol. Participants will utilize an electronic diary (eDiary) from Day -1 through to the Week 40 Follow-Up Visit. It is expected that participants will continue to use the eDiary utilized throughout the parent study. The eDiary may be either an application (app) that will be downloaded to the participant’s mobile smartphone or an eDiary device specifically designated for the purpose of collecting information as described below for participants who do not have a mobile smartphone or do not wish to download an app to their phone.

[908] Participants will be asked to capture the following information in their eDiary:

• Study IMP o Confirmation of dosing o Date and time of dosing o Number of capsules taken, with reasons not taken, if applicable

• Background Therapy (Emollient(s)) o Frequency of usage (number of times a day)

• Rescue Therapy Usage o Confirmation of usage

• Daily Peak Pruritus Numerical Rating Scale (PP-NRS) o Evaluation of worst itch over previous 24-hour period

• Daily Sleep Disturbance Numerical Rating Scale (SD-NRS) o Evaluation of sleep quality over previous 24-hour period

[909] Study staff will review the eDiary entries with participants at each visit. eDiaries will be reviewed for completeness and accuracy, and participants will be coached as needed on compliance with the protocol.

[910] At the Week 40 Follow-Up or Early Termination Visit (if applicable), the study staff will assist the participants to uninstall the eDiary application on their mobile smartphone devices and/or collect any eDiary devices that were distributed to the participants.

7.7. Drug Compliance

[911] Participants will use the eDiary to capture compliance with their study IMP. At specified visits per the Schedule of Activities (SOA), the study site staff will check numbers of used/unused capsules against diary entries and discuss with the participant the need to self-administer the capsules as directed, and to store the IMP according to label instructions.

[912] Prior to the specified study visits per the SOA, study site staff will call participants to remind them to bring all empty/partially used IMP wallets and cartons in the original containers to the study site for their visit.

[913] If a participant is found to be persistently noncompliant, the Sponsor, in conjunction with the Investigator, will decide as to whether the participant should be withdrawn from the study.

7.8. Dose Modification

[914] Dose adjustments, including dose interruptions, and/or decreasing the dose frequency may be allowed for safety or tolerability after consultation with the Medical Monitor. The maximum permitted interruption at one time is 14 consecutive days and the participants should have 80% compliance with IMP administration between any two visits after allowing for permitted interruptions. In cases where IMP was interrupted for less than 14 consecutive days, but overall compliance is below 80%, the possibility for discontinuation should be discussed with the Medical Monitor.

7.9. Concomitant Medications and Treatments

[915] Throughout the study, the participant may be prescribed concomitant medications or treatments deemed necessary to provide adequate supportive care at the discretion of the Investigator provided that the medications are licensed. However, it is the responsibility of the Investigator to confirm that details regarding the medication are recorded in full in the eCRF.

[916] All concomitant medications and/or treatments received by a participant should be recorded on the appropriate source document and eCRF with the following minimum requirements:

• Drug trade name

• Total daily dose

• Dates of administration

• Reason for use (indication)

• Dosage information (including dose and frequency)

[917] This will include all prescription drugs, herbal products, vitamins, minerals, over the counter (OTC) medications, and vaccines. Any changes in concomitant medications will also be recorded in the participant’s eCRF. The participant’s dosing eDiary may contain information relevant to the documentation of changes in concomitant medication.

7.9.5. Permitted Concomitant Medications and Treatments

[918] The following concomitant medications are permitted for use during the study:

• Concomitant medications for conditions other than AD may continue throughout the study, if not meeting any exclusion criteria, and should continue without change in dosage or formulation whenever possible.

• New therapy/treatments, not expected to have any impact on AD, but deemed necessary for the welfare of the participant during the study, are permitted. If there is doubt about their impact on AD or the ability of the participant to continue in the study, then this should be discussed with the Medical Monitor.

• Topical and oral antibiotics, antiviral, or antifungal therapy.

• Oral antihistamines.

• Nasal inhaled and ophthalmic corticosteroids.

• Non-replicating / non-live vaccines (Section 7.9.7 Immunizations).

[919] All participants must use an emollient at least twice daily throughout the study (Section 7.9.5.1 Background Therapy). 7.9.5.1. Background Therapy

[920] All participants must agree to continue with the use of an emollient at least twice daily. This must be a bland emollient which is additive-free, SLS-free, and fragrance- free and may be in cream, gel or ointment formulation. Whenever possible, the same brand and formulation of emollient should be used throughout the study by the participant. Participants are not allowed to use emollients containing additives (e.g., urea, ceramide, nicotinamide). Participants should continue this background emollient application twice daily until the Week 40 Follow-up Visit. Missed application of emollient will not be considered protocol deviation(s). On the day of the study visits, the participant will be asked to withhold the application of the emollient, and where safe, sunscreen and any other topical products until after all study assessments have been performed.

[921] Participants will record their background therapy via the participant eDiary from Day -1 to the Week 40 Follow-Up Visit (Section 7.6.4 eDiary).

7.9.5.2.Rescue Therapy

[922] If required, Investigators may prescribe/recommend prescription of rescue therapy for participants experiencing unacceptable worsening of atopic dermatitis. Additionally, individuals with uncontrolled atopic dermatitis could be at risk for a secondary skin infection. These participants may be prescribed an antimicrobial therapy to treat the infection as detailed below. Rescue therapy use is allowed throughout the entire study. There is no limit on the number of times that topical rescue therapy can be prescribed, although Investigators and participants may wish to consider whether the study is suitable for them if repeated courses are required.

[923] Rescue therapy, including microbial rescue therapy, should be prescribed as detailed below, and any specific deviations should first be discussed with the Medical Monitor. Participants rescued by such topical therapy will continue to take IMP and use of rescue therapy will be documented in the participant eDiary (Section 7.6.4 eDiary).

[924] Between Day -1 and Week 16, rescue therapy should be as follows:

[925] For non-sensitive body sites:

• Moderate potency (grade IV and V - Appendix 15.1) topical corticosteroids, twice daily for up to 7 days

[926] For sensitive sites e.g., head and neck:

• Topical tacrolimus (0.1%), topical pimecrolimus (1%) or grade VII topical corticosteroid, twice daily for up to 7 days [927] After Week 16, participants may be prescribed topical calcineurin inhibitors and/or topical corticosteroids of any potency for up to 7 days. It is advised that the lowest effective potency topical corticosteroid is chosen.

[928] If topical rescue therapy fails to control symptoms adequately, then the participant should be considered for alternative systemic therapy or phototherapy by the Investigator/their practitioner, at which point they will be classified as a treatment failure and IMP will be discontinued.

[929] For possible skin infection:

• Topical: o Appropriate courses of topical antimicrobial therapies, such as fucidic acid cream (e.g., Fucidin), mupirocin and/or bacitracin, are acceptable for use for skin infections, as required o If requiring concomitant moderate potency steroid therapy, fucidic acid with betamethasone 0.1% (as the valerate ester), (e.g., Fucibet cream) twice daily for up to 7 days

• Oral: o Appropriate course(s) of oral antibiotic(s) may be prescribed as per clinical need

7.9.6. Prohibited Concomitant Medications and Treatments

7.9.6.1. Prohibited Concomitant Medications

[930] 7.9.7Use of any of the following concomitant medications during the study require the IMP to be immediately discontinued where possible. If a participant requires treatment for atopic dermatitis with a prohibited concomitant medication during the study, they will be classified as a treatment failure:

• Topical Corticosteroids or Topical Calcineurin Inhibitors (unless used as Rescue Therapy, Section 7.9.5.2 Rescue Therapy)

• Topical PDE-4 Inhibitors

• Topical JAK Inhibitors

• Bleach baths

• Phototherapy treatment

• Tanning beds

• Systemic treatments that may lead to clinical improvements in atopic dermatitis, e.g., oral, or injectable corticosteroids, methotrexate, azathioprine, cyclosporine, mycophenolate mofetil, JAK inhibitors, biologic therapy, and other systemic immunosuppressive therapy (note single dose intra-articular or intra-lesional corticosteroid therapy is permitted).

• Leukotriene Receptor Antagonists

• Allergen Immunotherapy

• Live (attenuated) vaccinations: not permitted at any point during the study (Section

7.9.7 Immunizations).

7.9.7. Immunizations

[931] Non-replicating/non-live vaccines are permitted during the study. This includes all SARS-CoV-2 (COVID) non-live vaccines and non-replicating vaccines. The non-intranasal seasonal flu vaccine is permitted, as is the recombinant zoster vaccine (nonlive). However, the first dose of IMP should not be taken within a 7-day window of administration of the non-live vaccine or non-replicating vaccine.

[932] Live (attenuated) vaccinations are not permitted at any point during the study. This includes vaccines for measles, mumps, rubella, vaccinia, varicella, zoster (which contains the same virus as varicella vaccine but in much higher amount), yellow fever, rotavirus, and influenza (intranasal).

7.10. Blinding

[933] This is an open-label extension study with all participants taking Prevotella histicola Strain B capsules and as such no blinding is required for the study medication in this study.

[934] Investigators and participants will continue to be blinded to the participants treatment assignment in the parent study in order to minimize bias.

8. STUDY PROCEDURES BY VISIT

[935] No study procedures should be performed prior to the signing of the informed consent form (ICF). The ICF will need to be signed prior to any conducting any assessments at the Day -1 visit.

[936] Visit windows are consecutive calendar days and the target visit dates are calculated from the Day -1 visit.

[937] The Schedule of Activity (SOA) is presented in . An overview of each of the study assessments is presented in the subsections below. If a visit is not completed per protocol, it will be considered a missed visit. The site should still contact the participant by telephone to confirm that there have not been any adverse reactions. 8.11. Day -1 Visit

[938] The Day -1 visit may occur either the same day as the final treatment visit for the parent study, or within 7 days of completing the treatment period of the parent study. If a participant’s Day -1 Visit occurs on the same day as the end of treatment visit of the parent study, then any study assessments performed at the final treatment visit of the parent study do not need to be repeated (See ).

[939] Each site will sequentially assign a unique identifier to each participant that will be used for the duration of the study.

[940] On the day of the visit the participant will be asked to withhold the application of the emollient, and where safe, sunscreen and any other topical products until after all study assessments have been performed (Section 7.9.5.1 Background Therapy).

[941] The following procedures will be performed on the Day -1 Visit:

• Obtain written informed consent from participant

• Assessment of inclusion and exclusion criteria

• Collection of demographics including year of birth, age, gender, race, and ethnicity

• Review of changes in medical history and smoking status from the baseline visit of the parent study

• Full physical examination

• Vital signs (blood pressure, heart rate, respiratory rate, and temperature) including height and weight measurements BMI will be calculated using the participant’s height and weight.

• 12-lead electrocardiogram (ECG)

• Blood sample collection for safety labs

• Urine sample collection for pregnancy testing for women of childbearing potential (WOCBP), and for urinalysis

• AD rating scales - vIGA, EASI, BSA, and SCORAD

• Patient reported clinical rating scales - POEM, DLQI and ADCT

• PP-NRS and SD-NRS scores in participant diary

• Digital photographs of the upper and lower body (anterior and posterior) as half body shots. Additional photographs of up to six specific body areas, i.e., limbs, trunk and back (excluding scalp, genitals, and any identifying features) may also be taken

• Review and document concomitant medications and therapies • Assess and document adverse events (AEs) that occur after participant signs informed consent form (ICF)

[942] The participant will be instructed by the investigator or study staff to continue to use their emollient as per protocol requirements.

Enrollment Procedures

• Enroll the participant in IRT after all Day -1 activities are completed and the participant is still deemed eligible to participate.

• If the participant was in Cohort 3 of the parent study and is deemed eligible for this study, they will be randomized 1 : 1 to receive either 1.6xlO^u total cells of Prevotella histicola Strain B, or 6.4xlOⁿ total cells of Prevotella histicola Strain B in this study. An IRT will be used for assigning eligible participants from this cohort into to a dosing group in this study. Sufficient IMP will be dispensed to cover the first 4 weeks of the treatment period. The participant will be instructed to take their first dose of IMP at home on Day 1 of the study.

• Assist the participant in the transitioning of apps into this study eDiary on their smartphone device and provide instructions on completion of eDiary.

8.12. Treatment Period (Week 4 - Week 36)

[943] These visits will take place approximately every month from Week 4 until Week 16, and approximately every 2-4 months from Week 16 until Week 36. Participants may dose at home on the day of the treatment period visits. Prior to these visits, the participant will be asked to withhold the application of the emollient, and where safe, sunscreen, and any other topical products until after all study assessments have been performed. See Section 7.9.5.1 Background Therapy.

[944] The following procedures will be performed at each visit during this period:

• Brief physical examination (excluding Week 36 which will consist of a full physical examination)

• Vital signs including weight measurement

• 12-1 ead ECG

• Urine sample collection for pregnancy testing (women of childbearing potential only)

• Blood sample collection for safety labs

• Blood sample collection for biomarkers (Week 36/Early Termination only)

• Urine for urinalysis

• Digital photographs of the same lesions/ body area taken at the Day -1 Visit • AD rating scales - vIGA, EASI (and BSA), and SCORAD

• Patient reported clinical rating scales - POEM, DLQI and ADCT

• Collection and or review PP-NRS and SD-NRS scores in participant diary

• Review and documentation of concomitant medications and therapies including emollient use

• Assessment and documentation of adverse events (AEs)

• Review of participant compliance with IMP administration and use of eDiary

• Collection and reconciliation of returned IMP, i.e., IMP accountability. Participants will be required to return all empty cartons and any remaining IMP at the Week 36 visit

• Dispensation of IMP (Excluding Week 36 i.e., the End of Treatment visit)

8.13. Week 40 Follow Up/ End of Study Visit

[945] This visit will be the last visit in the study and will take place approximately 4 weeks after the last dose of IMP. Prior to this visit, the participant will be asked to withhold the application of the emollient, and where safe, sunscreen, and any other topical products until after all study assessments have been performed. See Section 7.9.5.1 Background Therapy.

[946] The following procedures will be performed:

• Brief physical examination

• Vital signs including weight measurements

• 12-1 ead ECG

• Blood sample collection for safety labs

• Urine sample collection for urinalysis

• Digital photographs of the same lesions/body area taken at the Day -1 Visit

• AD rating scales - vIGA, EASI (and BSA), and SCORAD

• Patient reported clinical rating scales - POEM, DLQI and ADCT

• Collection and or review of PP-NRS and SD-NRS scores in participant diary

• Review of and documentation of concomitant medications and therapies including emollient use

• Assessment and documentation of adverse events (AEs)

• Removal of eDiary application from smartphone/ collection of eDiary device 8.14. Early Termination Visit

[947] Participants who withdraw prematurely from the study should have an early termination visit using the Early Termination Visit schedule within 14 days of asking to withdraw consent or within 72 hours of starting any AD therapy if their withdrawal was due to treatment failure. The Early Termination Visit will consist of the same assessments and procedures as the End of Treatment Study Visit at Week 36. Once all assessments are complete, study staff will assist the participant to uninstall the mobile application from their smartphone device. The participant will also be asked to have a final telephone call 28 days (+3 days) after taking their last dose of IMP for safety assessments. The date of this telephone call will be considered the end of study date for these participants.

8.15. Unscheduled Visits

[948] Unscheduled visits are visits that fall outside of the scheduled visits indicated in the SOA. These visits and the findings are to be recorded on the appropriate eCRFs.

8.16. COVID-19 Pandemic

[949] Parts or all of this study are expected to run during the CO VID-19 pandemic. As a result, a thorough risk analysis has been carried out. In addition, a number of mitigation steps have been considered, for example, the scenarios of individual selfisolation or local/national lockdown.

8.16.8. Prevotella histicola Strain B and Risk of COVID-19 Infection

[950] Prevotella histicola Strain B does not broadly impair either innate or adaptive immune responses, as detailed in a full risk-assessment in Appendix 15.3. Antiviral responses such as cytotoxic T-cell production of interferon-gamma, innate anti-viral production of interferon-alpha and interferon-beta, and the generation of high-affinity antibodies are all preserved pre-clinically after treatment with Prevotella histicola Strain B. There is no pre-clinical or clinical evidence of Prevotella histicola Strain B causing immunosuppression.

8.16.9. Prevotella histicola Strain B and COVID-19 Vaccination

[951] As detailed in Section 7.9.7 Immunizations of this protocol, live and live- attenuated vaccines should not be given with Prevotella histicola Strain B. Non-live and non-replicating vaccines are permitted, and it is not expected that the safety of participants will be impacted by their co-administration. The efficacy of the vaccines co-administered with Prevotella histicola Strain B has not been tested. 8.16.10. This Study and COVID-19 Infection

[952] Self-isolation or a positive COVID-19 test in a well participant may not be a reason in itself to stop dosing since Prevotella histicola Strain B is not expected to increase the risks associated with COVID-19. If a study participant is diagnosed with COVID-19 infection (diagnosed clinically or by laboratory tests), the participant may continue study treatment if the Investigator considers that there is a positive individual risk/benefit balance. This should be discussed with the Medical Monitor.

8.16.11. COVID-19 Mitigation Steps

[953] If a participant with COVID-19 must self-isolate or quarantine while on study, and a study visit coincides with this self-isolation or quarantine, the study visit will be missed and the reason the visit was not done recorded in the source documents with COVID-19 isolation/lockdown as the reason for the visit not completed.

[954] In lieu of the study visits, the participant should receive a telephone call to assess adverse reactions, ascertain study IMP status (i.e., did the participant self-interrupt taking IMP) and emollient usage, and collect information on any concomitant medications, including any rescue therapy. Information should be recorded in the participant’s source documents and entered into the EDC, as applicable.

[955] The participant must try and attend all study visits; however, the Week 16 and Week 36 study visit should not be missed wherever possible. These visits, therefore, may be conducted outside of the protocol study window. Please contact the Medical Monitor to discuss further.

8.17. Missed Visits and Procedures

[956] Missed visits and any procedures not performed (not attempted) for reasons other than screen failure, illness, injury, or progressive disability (i.e., the participant is physically unable to perform test) will be reported as protocol deviations.

[957] Procedures or visits not performed due to screen failure, illness, injury, or disability, including procedures that were attempted but failed (i.e., blood samples unable to be drawn after multiple attempts) will not be reported as protocol deviations.

9. EFFICACY ASSESSMENTS

[958] Assessments will be performed at designated time-points throughout the study for efficacy evaluations. In addition to the assessments below, participants will provide any updates to the existing information on their demographics and smoking history,

\T1 past medical history (including diagnosis of atopic dermatitis), as well as concomitant medication usage.

[959] All efficacy assessments will be completed at the study site utilizing a site tablet at the specified visits as indicated on the SOA. The participants will be trained on how to complete the assessments that are considered patient reported outcomes (PRO). PROs should be completed prior to conducting any assessments with the exception of signing the consent form on Day-1. The same reviewer should conduct the skin assessments for a single participant at each visit wherever possible, and at a minimum for the Day -1, Week 16, and Week 36 assessments.

[960] The Investigators and site staff will be provided with further details on how to perform the following assessments and how to calculate each of the scores (if applicable).

9.18. Eczema Area and Severity Index

[961] The Eczema Area and Severity Index (EASI) is a validated measure of eczema severity, which considers a combination of the body surface area affected across 4 body regions, and the severity of the clinical signs of erythema, oedema/induration, excoriation and lichenification (Eczema, n.d.). The EASI score ranges from 0 - 72 (EASI, 2017 Jan). EASI-50, EASI-75, EASI-90 responses are defined as at least 50%, 75% and 90% decrease from baseline EASI score respectively.

9.19. Validated Investigator’s Global Assessment

[962] The Validated Investigator Global Assessment scale for Atopic Dermatitis (vIGA-AD) will be used to describe the overall appearance of lesions at a given time-point (Simpson E, 2020 Sep). There is a standardized grading system based on an overall assessment of the degree of erythema, papulation/induration, lichenification, and oozing/crusting. In indeterminate cases, extent will be used to differentiate between scores - but otherwise extent is not used in the scoring system. The vIGA score ranges from 0 (Clear skin) to 4 (Severe disease).

9.20. SCORing Atopic Dermatitis

[963] The SCORing Atopic Dermatitis (SCORAD) is a clinical tool which is also used to assess the extent and severity of eczema, to assess treatment effects. There is an investigator-rated area score which uses the rule of nines to assess disease extent, and a disease intensity score comprising erythema, swelling, oozing/crusting, excoriation, lichenification, and dryness. Additionally, there is a subjective symptoms component which considers itch and sleeplessness scored using a visual analogue scale. These scores combine to give a SCORAD score between 0 - 103 (Dermatitis, 1993).

9.21. Patient Oriented Eczema Measure

[964] The Patient Oriented Eczema Measure (POEM) is a simple PRO assessment tool for monitoring disease severity. It includes a series of 7 questions, measuring itch, sleep, bleeding, weeping/oozing, cracking, flaking, and dryness/roughness over the last week, and is scored by the participant. Each of the 7 questions is scored from 0 (no days) to 4 (every day), giving a POEM score range from 0 to 28, with higher scores representing higher disease severity Charman, 2004 and Charman, 2013). The minimally clinically important difference threshold is a change of > 3.4 points on average (Schram, et al., 2011). For the purposes of changes within an individual participant, a response will therefore be considered to be a > 4-point change from baseline.

9.22. Dermatology Life Quality Index

[965] The Dermatology Life Quality Index (DLQI) is a validated PRO instrument comprised of 10 questions to assess how a participant’s skin disease has affected their quality of life over the previous week (Finlay AY, 1994). The DLQI score ranges from 0 to 30, with higher scores indicating greater impairment of quality of life. A DLQI score of 0 or 1 is considered as having no effect on a participant’s quality of life, and a 4-point change from baseline is considered the minimal clinically important difference threshold (Basra, 2015).

9.23. Peak Pruritus Numerical Rating Scale (PP-NRS)

[966] The Peak Pruritus Numerical Rating Scale (PP-NRS) is a scale from 0 (“no itch”) to 10 (“worse imaginable itch”) for participants to rate the worst itch they have experienced over the previous 24 hours (Phan, 2011). The PP-NRS will be completed daily via a daily questionnaire from the Day-1 Visit to the Week 40 visit. A > 2-4-point change from baseline is considered the minimally clinically important difference threshold (Yosipovitch, et al., 2019).

9.24. Sleep Disturbance Numerical Rating Scale (SD-NRS)

[967] The Sleep Disturbance Numerical Rating Scale (SD-NRS) is a scale from 0 (“best possible sleep”) to 10 (“worse possible sleep”) for participants to rate the worst sleep they have experienced over the previous 24 hours. The SD-NRS will be completed via a daily questionnaire from the Day-1 Visit to the Week 40 visit. A > 2 point change from baseline is considered the minimally clinically important difference threshold (Dias- Barbosa, Matos, & Vernon, 2020).

9.25. Body Surface Area

[968] The Body Surface Area (BSA) is a measure of the extent of atopic dermatitis at a given time. It is calculated by estimating the amount of active atopic dermatitis using the number of participant’s handprints, where one handprint (including digits) represents 1% body surface area. The BSA provides another assessment of disease severity by looking at coverage of body surface and is sometimes assessed as a product of the IGA*BSA as a further marker of disease severity and response to treatment (Suh, 2020).

9.26. Atopic Dermatitis Control Tool

[969] The Atopic Dermatitis Control Tool (ADCT) is a 6-question PRO instrument used to detect change of disease activity in a person over time. There are six main areas that assess the multi-dimensional aspects of disease control over the course of a week, scored between 0-4, with a minimum score of 0 and a maximum score of 24. A higher score indicates lower AD control. A change of 5 points is the threshold for meaningful within person change, where a decrease of 5 or more points indicates clinically relevant improvement of AD control and an increase of 5 or more points indicates a clinically relevant worsening of AD control (Pariser, 2020).

10. SAFETY ASSESSMENTS

[970] The adverse event (AE) definitions and reporting procedures provided in this protocol comply with all applicable regulations and International Conference on Harmonization (ICH) guidelines. The Investigator will carefully monitor each participant throughout the study for possible adverse events.

10.27. Adverse Events

[971] An adverse event (AE) is any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with a study, use of a drug product or device whether or not considered related to the drug product or device.

[972] Signs or symptoms of the condition/disease for which the IMP is being studied should be recorded as AEs only if their nature changes considerably or their frequency or intensity increases in a clinically significant manner as compared to the clinical profile known to the investigator from the participant’s history or from Day -1. 10.27.12. Adverse Events of Special Interest

[973] There are no prespecified AEs of special interest (AESI) for this study.

10.28. Adverse Drug Reactions

[974] Adverse drug reactions (ADR) are all noxious and unintended responses to a medicinal product related to any dose. The phrase “responses to a medicinal product” means that a causal relationship between a medicinal product and an adverse event is at least a reasonable possibility, i.e., the relationship cannot be ruled out. Therefore, a subset of AEs can be classified as suspected ADRs, if there is a causal relationship to the medicinal product. A suspected unexpected serious adverse reaction (SUSAR) is another subset of ADR, which includes all adverse reactions that are suspected to be related to an investigational medicine product and are both serious and unexpected.

10.29. Serious Adverse Events

[975] A serious adverse event (SAE) is defined as an adverse event that meets any of the following criteria:

• Results in death.

• Is life-threatening that is, poses an immediate risk of death as the event occurred.

- This serious criterion applies even if the participant, in the view of the Investigator or Sponsor, is at immediate risk of death from the AE as it occurs. It does not apply if an AE hypothetically might have caused death if it were more severe.

• Requires inpatient hospitalization or prolongation of existing hospitalization.

- A participant admitted to a hospital, even if he/she is released on the same day, meets the criteria for the initial inpatient hospitalization. An emergency room visit that results in admission to the hospital would also qualify for the initial inpatient hospitalization criteria. However, emergency room visits that do not result in admission to the hospital would not qualify for this criterion and, instead, should be evaluated for one of the other criteria in the definition of serious (e.g., life-threatening adverse experience, important medical event).

- Hospitalizations for reasons not associated with the occurrence of an AE (e.g., preplanned surgery or elective surgery for a pre-existing condition that has not worsened or manifested in an unusual or uncharacteristic manner) do not qualify for reporting.

° For example, if a participant has a condition recorded on his/her medical history and later has a preplanned surgery for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, since there is no AE upon which to assess the serious criteria.

° Please note that, if the pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, this would then qualify as an AE and, if necessary, the seriousness of the event would need to be determined.

• Results in persistent or significant disability or incapacity.

- This serious criterion applies if the “disability” caused by the reported AE results in a substantial disruption of the participant’s ability to carry out normal life functions.

• Results in a congenital anomaly or birth defect in the offspring of the participant (whether the participant is male or female).

• Is an important medical event that, based upon appropriate medical judgment, may jeopardize the participant, and may require medical or surgical intervention to prevent one of the other outcomes listed in the definition of serious.

- Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias that do not result in inpatient hospitalization, or the development of drug dependency or drug abuse.

10.30. Reporting and Recording AEs

[976] The Investigator will carefully monitor each participant throughout the study for possible AEs. In order to confirm complete safety data collection, all AEs occurring during the study (i.e., after the signing of the Informed Consent form) must be reported in the CRF. AEs reported during the parent study that are ongoing at the end of treatment visit will continue to be followed up during this study until resolution or the participants completes the study, whichever is first.

[977] All AEs will be collected and reported in the electronic data capture (EDC) system and compiled into reports for periodic reviewing by the Medical Monitor. The Medical Monitor shall promptly review all information relevant to the safety of the investigational product, including all serious adverse events (SAEs). Special attention will be paid to those that result in permanent discontinuation of the investigational product being studied, whether serious or non-serious.

[978] If the investigator learns of any SAE, including a death, at any time after a participant has been discharged from the study, and he/she considers the event to be reasonably related to the IMP or study participation, the investigator must immediately notify the sponsor (or designee). [979] Serious AEs that occur more than 30 days after the last dose of IMP need not be reported unless the investigator considers them related to the IMP.

10.30.13. Assessment of AEs

[980] Adverse events will be solicited in a consistent manner at every study visit. At every study visit, participants will be asked uniform open-ended questions to elicit any medically related changes in their well-being. They will also be asked if they have been hospitalized, had any accidents, used any new medications, changed concomitant medication regimens (prescription or OTC medications), noticed any changes in bowel habits or had unplanned visits to their general practitioner since the last visit.

[981] In addition to participant observations, AEs identified from any study data (e.g., laboratory values, physical examination findings, ECG changes) or identified from review of other documents (e.g., participant diaries) that are relevant to participant safety and considered clinically significant will be documented on the AE page in the CRF.

[982] If the participant reports an adverse event, the following will be recorded in the source and on the eCRF :

1. Description of the event

2. Date and time of onset and resolution (duration)

3. CTCAE v5.0 grade (Grade 1 - 5)

4. Seriousness (does the event meet the above definition for an SAE)

5. Causality, relation to investigational product

6. Action taken regarding investigational product

7. Outcome

8. If any Concomitant Medications were given due to the AE

9. Whether the AE resulted in participant withdrawal from the study

10. Investigator-specified assessment if the AE is related to a recent/current COVID infection

11. If a CO VID positive PCR test received within the last 14 days

[983] Signs or symptoms of a participant’s atopic dermatitis should be recorded as AEs only if their nature changes considerably or their frequency or intensity increases in a clinically significant manner as compared to the clinical profile known to the Investigator from the participant’s history. 10.30.14. Assessment of Severity

[984] The severity, or intensity, of an AE refers to the extent to which an AE affects the participant’s daily activities or their health. The intensity of the AE will be rated in accordance with the CTCAE Version 5.0. Adverse events related to temperature and abnormal laboratory results that are not found in the CTCAE Version 5.0 will be rated in accordance with the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials [Appendix 15.4 Toxicity Grading ScaleToxicity Grading Scale].

[985] Changes in the severity of an AE should be documented to allow an assessment of the duration of the event at each level of intensity to be performed. Adverse events characterized as intermittent do not require documentation of onset and duration of each episode.

10.30.15. Assessment of Causality

[986] The investigator’s assessment of an AE’s relationship to IMP is part of the documentation process. Regardless of the investigator's assessment of an AE's relationship to IMP, the AE must be reported.

The relationship or association of the IMP in causing or contributing to the AE will be characterized using the following classification and criteria:

Unrelated: There is no association between the IMP and the reported events.

Possible: Treatment with the IMP may have caused or contributed to the AE, i.e., the event follows a reasonable temporal sequence from the time of drug administration or follows a known response pattern to the IMP but could also have been produced by another factor.

Probable: A reasonable temporal sequence of the event with drug administration exists and based upon the known pharmacological action of the drug, known or previously reported adverse reactions to the drug or class of drugs, or judgment based on the investigator’s clinical experience, the association of the event with the IMP seems likely. The event disappears or decreases on cessation or reduction of the dose of IMP.

Definite: A definite causal relationship exists between drug administration and the

AE, and other conditions (concurrent illness, progression/expression of disease state, or concurrent medication reaction) do not appear to explain the event. The event reappears or worsens if the IMP is re-administered. 10.30.16. Description of Adverse Events

[987] When recording an AE, the Investigator should use the overall diagnosis or syndrome using standard medical terminology, rather than recording individual symptoms or signs. The eCRF and source documents should be consistent. Any discrepancies between the participant’s own words on his/her own records (e.g., diary card) and the corresponding medical terminology should be clarified in the source documentation.

[988] Details for completion of the Adverse Event eCRF are described in the eCRF Completion Guidelines.

10.31. Reporting Serious Adverse Events

[989] Serious Adverse Events (SAEs) must be reported to the Medical Monitor and Sponsor immediately, without undue delay but no later than within 24 hours of the site learning of the SAE.

[990] To report the SAE, the investigator must record the SAE on the AE eCRF in the EDC system as well as any relevant CRF forms (e.g., drug dispensation CRF, applicable laboratory CRF). When the AE CRF is completed, Medpace Safety personnel will be automatically notified electronically and will retrieve the form.

10.31.17. Follow Up of Adverse Events

[991] All AEs must be followed to satisfactory resolution, until the Investigator deems the event to be chronic or not clinically significant, the event is considered stable, the participant dies, or the participant is lost to follow-up. However, any new AEs that start more than 28 days after the final dose and changes in AEs that occur after the participant’s end of study visit will not be recorded in the eCRF.

10.32. Pregnancy

[992] Pregnancy is not regarded as an AE unless there is a suspicion that an IMP may have interfered with the effectiveness of a contraceptive medication. Any pregnancy that occurs during study participation or up to 28 days after the final dose of IMP must be reported to Medpace Clinical Safety by phone or email, within 2 weeks of learning of its occurrence. Medpace Clinical Safety will send the Exposure in Utero Form to the site for completion within 24 hours. This form should be completed and returned to Medpace Clinical Safety within 24 hours of receipt.

[993] All SAEs occurring in association with a pregnancy, brought to the Investigator’s attention after the participant has completed the study must be promptly reported to Medpace Clinical Safety. Please see Appendix 15.2 Contraceptive Guidance and Collection of Pregnancy

Information for further information.

10.33. Overdose

[994] Excessive dosing (greater than a total of four (4) capsules within 24 hours) should be recorded in the CRF. Participants will be instructed to contact the Investigator or study coordinator immediately in the event of a suspected overdose.

[995] Any confirmed overdose must be promptly reported to Medpace Clinical Safety via the Special Situations Form. Overdose itself is not to be reported as an AE: however, any AEs or SAEs associated with the overdose are to be reported on relevant AE/SAE sections in the eCRF and on the Paper SAE Form provided to Medpace Clinical Safety (Section 10.31 Reporting Serious Adverse Events).

[996] In the event of a symptomatic overdose, the Investigator should:

7. Manage the participant symptomatically with supportive care

8. Contact the Medical Monitor urgently

9. Document the quantity of the excess dose in the eCRF

10. Document the overdose symptoms and their duration in the eCRF

[997] Doses of Prevotella histicola Strain B capsules that have previously been administered in participants with atopic dermatitis include a dose of 8.0 x 10¹¹ cells taken once daily for 16 weeks, and 1.28 x 10¹² cells taken once daily for 8 weeks. There are no specific adverse events expected in an overdose; however, the participant should be closely and carefully monitored. There is no specific treatment or antidote, but supportive clinical care should be provided as dictated by the participant’s clinical status.

[998] Decisions regarding dose interruptions or modifications will be made by the Investigator in consultation with the Medical Monitor based on the clinical evaluation of the participant.

10.34. Safety Signal Detection

[999] Selected data from this study will be reviewed periodically to detect as early as possible any safety concem(s) related to the IMP so that Investigators, participants, regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible.

[1000] The Medical Monitor or medically qualified designee/equivalent will conduct an ongoing review of SAEs. PPD DM will perform ongoing SAE reconciliations in collaboration with the PV representative. [1001] As appropriate for the stage of development and accumulated experience with the IMP, medically qualified personnel at the Sponsor may identify additional safety measures (e.g., AEs, vital signs, laboratory, or ECG results) for which data will be periodically reviewed during the course of the study.

10.35. Study Halting Criteria

[1002] The study will be halted if any of the following occur:

• One or more SAE considered definitely or probablyrelated to the investigational product.

• Two or more participants with a SAE of the same type considered definitely or possibly related to the investigational product.

• Three or more participants with grade 3 AEs of the same type considered definitely, probably, or possibly related to the investigational product.

• Any participant develops a documented Prevotella histicola infection in a sterile space confirmed by clinical culture and/or qPCR.

10.36. Laboratory Measurements

[1003] Standard laboratory analyses to understand safety and tolerability include the following measurements:

For WOCBP, urine pregnancy testing will be conducted at each study visit.

[1004] Additional testing may be ordered if needed, to further assess an adverse event (AE), or if there is any suspicion that a participant may be pregnant, throughout the course of the study.

[1005] Only abnormal laboratory test results (hematology, clinical biochemistry, or urinalysis) or other safety assessments (e.g., ECGs, vital sign measurements), which are clinically significant in the medical and scientific judgment of the investigator, are to be recorded as AEs or SAEs.

[1006] A central laboratory will be used for all laboratory analyses. Details of sample collection and handling procedures will be provided in the specific laboratory manual.

10.36.18. Review of Laboratory Measurements

[1007] The Investigator must complete a timely review of the laboratory reports, document this review, and record any clinically relevant changes occurring during the study. If the laboratory reports are not transferred electronically, the values must be filed with the source information (including reference ranges). In most cases, clinically significant abnormal laboratory findings are those that are not associated with the underlying disease, unless judged by the Investigator to be more severe than expected for the participant's condition.

[1008] All laboratory tests with values considered clinically significantly abnormal during participation in the study or within 30 days after the last dose of IMP should be repeated until the values return to normal or baseline value or are no longer considered clinically significant by the Investigator or Medical Monitor. If such values do not return to normal/baseline within a time judged reasonable by the Investigator, the etiology should be identified, and the Sponsor notified.

[1009] All protocol-required laboratory assessments, as defined in this section, must be conducted in accordance with the laboratory manual and the SOA. If laboratory values from non-protocol specified laboratory assessments performed at the institution’s local laboratory require a change in participant management or are considered clinically significant by the Investigator (e.g., SAE or AE or dose modification), then the results must be recorded on the Adverse Events eCRF.

10.36.19. Blood Volumes

[1010] The planned maximum amount of blood collected from each participant over the duration of the study, including any extra assessments that may be required, will not exceed 100 mL. Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the samples. The planned maximum amount of blood collected from each participant at a single visit will not exceed 20 mL, and the planned maximum amount of blood collected from each participant over 30 days will not exceed 20 mL.

10.37. Biomarkers

10.37.20. Immune Protein Biomarkers

[1011] Immunoglobulin E (IgE) are antibodies produced by the immune system and are often raised in patients with AD, particularly with the phenotype known as ‘extrinsic’ AD (Renert- Yuval, 2021). IgE is a recognized biomarker of disease severity in AD and is regularly measured in clinical practice. It is being measured in participants to see if treatment response can be predicted by Day 1 IgE level, and also whether IgE levels improve on treatment as a biomarker of treatment success. In addition to the IgE levels, other immune protein markers such as cytokines may be measured from this sample in order to assess the anti-inflammatory and disease-modifying effects of Prevotella histicola Strain B. These samples will be collected at the end of study visit of the parent study and at Week 36/Early Termination Visit of this study.

10.37.21. Transcription Analysis

[1012] RNA will be collected from whole blood samples at the end of study visit of the parent study and at Week 36/Early Termination Visit of this study to quantify inflammation markers in immune cells to assess the effect of Prevotella histicola Strain B. These samples may be analyzed subject to the clinical data in the trial. The genes to be analyzed may include those related to host immune response as well as those related to the disease pathology.

10.38. Other Safety Measurements

10.38.22. Vital Signs, Height and Weight

[1013] Vital signs will be obtained after the participant has been in a seated position for approximately 5 minutes. Vital signs, including systolic and diastolic blood pressure, pulse rate (radial artery )/minute, respiratory rate/minute, and temperature. Height will be measured and recorded at the Baseline Visit of the parent study only. Weight will be assessed at specified visits (without shoes and outdoor wear e.g., coats). Body mass index will be calculated from the height and weight. Investigators should pay special attention to clinical signs related to previous serious illness.

10.38.23. Physical Examination

[1014] A physical examination (PE) will be performed and recorded in source at specified visits. Only abnormal, clinically significant findings will be recorded as AEs on the eCRF.

[1015] The following systems will be examined when a full PE is indicated: general appearance, cardiovascular, lungs, abdomen, musculoskeletal, central nervous system, lymph nodes and skin.

[1016] The following systems will be examined when a brief PE is indicated: general appearance, cardiovascular, lungs, abdomen, and skin.

10.38.24. 12-Lead Electrocardiogram

[1017] A single 12-lead electrocardiogram (ECG) will be obtained at specified visits using an ECG machine that automatically calculates heart rate and measures PR, RR, QRS, QT and QTcF (Fridericia) intervals.

[1018] A single ECG tracing is to be obtained on the day of the visit after the participant has been in a lying position for approximately 5 minutes. If in the opinion of the Investigator, there appear to be clinically significant findings, it should be repeated. If the repeated tracing also appears clinically significant, the Investigator should report the abnormality as an AE and consult with the Medical Monitor to decide whether the participant should continue treatment in the study.

10.39. Non-Safety Measurements

10.39.25. Digital Photography

[1019] Digital photographs should be taken of the upper and lower body (upper & lower anterior and upper & lower posterior) as half body shots. Additional photographs of up to six specific body areas, i.e., limbs, trunks, and back, will also be taken. The same locations photographed in the parent study should be followed through this study for each participant.

[1020] Procedural details for digital photography will be provided to the sites. 11. STUDY MANAGEMENT AND ADMINISTRATION

11.40. Adherence to protocol

[1021] A deviation from the protocol is an unintended or unanticipated departure from the procedures or processes approved by the Sponsor and the IRB/IEC and agreed to by the Investigator. A significant deviation occurs when there is non-adherence to the protocol or to local regulations or ICH GCP guidelines that may or may not result in a significant, additional risk to the participant or impacts the integrity of study data.

[1022] The Investigator should not deviate from the protocol. However, the Investigator may implement a deviation from, or a change of, the protocol to eliminate an immediate hazard/safety risk to study participants without prior IRB/IEC approval. As soon as possible after such an occurrence, the implemented deviation or change, the reasons for it, and any proposed protocol amendments should be submitted to the IRB/IEC for review and approval, to the Sponsor for agreement, and to the regulatory authorities, where required. The deviation should be well documented in the participant’s source documentation.

[1023] In order to keep deviations from the protocol to a minimum, the Investigator and relevant site personnel will be trained in all aspects of study conduct by the Sponsor or Sponsor representative. This training will occur either as part of the Investigator’s Meeting or Site Initiation Visit (SIV). Ongoing training may also be performed throughout the study during routine site monitoring activities.

11.41. Monitoring

11.41.26. Definition of Source Data

[1024] Source documents are original records in which raw data are first recorded. These may include hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, pharmacy records, care records, ECG, or other printouts, completed scales, quality of life questionnaires, certified copies, or video, for example. Source documents should be kept in a secure, limited access area.

[1025] All source documents must be accurate, clear, unambiguous, permanent, and capable of being audited. They should be made using some permanent form of recording (ink, typing, printing, optical disc). They must not be obscured by correction fluid or have temporary attachments (such as removable self-stick notes). Photocopies and/or printouts of CRFs are not considered acceptable source documents. 11.41.27. Source Data Verification

11.42. Data Management

11.42.28. Data Quality Assurance

[1026] This study will be conducted according to ICH E6(R2) risk and quality processes described in the applicable procedural documents.

11.42.29. Data Entry and Reconciliation

Case Report forms/extemal electronic data will be entered/loaded into a validated electronic database that is validated and compliant with US Title 21 CFR Part 11.

11.42.30. Audit and Inspection

[1027] The Investigator will permit study-related audits mandated by the Sponsor, after reasonable notice, and inspections by domestic or foreign regulatory authorities.

11.43. Good Clinical Practice

[1028] Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action by the Sponsor to secure compliance. Continued noncompliance may result in the termination of the site’s involvement in the study.

12. STATISTICS

[1029] A description of statistical methods follows and will be described in more detail in the Statistical Analysis Plan.

12.44. General Statistical Considerations

[1030] Statistical analysis will be performed using SAS software Version 9.3 or later.

[1031] Baseline will be defined as the baseline value taken from the parent study. In some cases, change prior to first dose of Prevotella histicola Strain B and change since first dose in this study may also be analyzed.

[1032] Summaries may be presented using any of the following as applicable to the endpoint of interest:

• Overall and by treatment group in this study

• By treatment groups in this study and the parent study o All placebo treatment groups will be pooled o Prevotella histicola Strain B treatment groups may be pooled or shown by total daily dose, formulation and/or dose frequency

• By parent study, overall and by treatment group as above 12.45. Definition of Analysis Sets and Defined Data Point Sets

[1033] The following analysis sets will be used in the statistical analyses.

12.45.31. Participant Analysis Sets

[1034] Enrolled set: The enrolled set will consist of all participants who sign the ICF.

[1035] Full analysis set (FAS): The FAS set will consist of all participants who received at any IMP under this protocol.

[1036] Other parent study specific analysis sets may also be used in interim analyses which will be defined by the subset of participants from the FAS who were previously enrolled from the specified parent study or studies.

12.45.32. Defined Data Point Sets

[1037] The following data point sets (DPS) are defined:

DPS1 : Consists of all observed data collected following first dose of IMP under this protocol until the 28 days after the last dose of IMP.

DPS2: Consists of all observed data collected following first dose of IMP in the parent study protocol until 28 days after the last dose of IMP under this protocol.

DPS3: Consists of all observed data collected at a scheduled visit in this protocol.

DPS3a: Is a subset of DPS3, excluding any data collected within 4 weeks after the use of permitted rescue medications or at any time after the use of prohibited medications for atopic dermatitis.

DPS3b: Is a subset of DPS3, where data collected within 4 weeks after the use of permitted rescue medications or at any time after the use of prohibited medications for atopic dermatitis will be replaced by ‘non-responder’ for response endpoints or the last observation carried forward for continuous endpoints.

DPS4: Consists of all observed data collected at a schedule visit in this study or the parent study.

DPS4a: Is a subset of DPS4, excluding any data collected within 4 weeks after the use of permitted rescue medications for atopic dermatitis.

DPS4b: Is a subset of DPS4, where data collected within 4 weeks after the use of permitted rescue medications for atopic dermatitis has been replaced by ‘non-responder’ for response endpoints or the last observation carried forward for continuous endpoints. [1038] The FAS with DPS1 and DPS2 will be used to estimate the primary estimands around adverse events, together with estimands based on endpoints looking at use of rescue medications.

[1039] The FAS with DPS3, DPS3a, DPS3b, DPS4, DPS4a and DPS4b will be used to estimate efficacy endpoints where data is collected at specific timepoints.

[1040] The FAS with DPS3 and DPS4 will be used to estimate safety endpoints where data is collected at specific timepoints.

[1041] The parent study-specific endpoints will be used instead of the FAS for interim analyses based on participants taken from a specific study or studies.

12.46. Estimands and Intercurrent Events

12.46.33. Primary Estimand of the Primary Objective

[1042] Population: The FAS will be used for all primary estimands. Note that for interim analyses, a parent study specific analysis set may be used in place of the FAS.

[1043] The primary efficacy variables will be the incidence and rate per 100 patient- years of TEAEs. Both the period defined by this study alone and the period defined by this study and the relevant parent study will be reported.

[1044] Subgroups of TEAEs will be evaluated as follows:

• All TEAEs

• TEAEs of Grade 2 or above

• TEAEs of Grade 3 or above

• Serious TEAEs

• Fatal TEAEs

• TEAEs causing discontinuation of study drug

• Study drug related TEAEs of Grade 2 or above

• Study drug related TEAEs of Grade 3 or above

• Study drug related serious TEAEs

• Study drug related fatal TEAEs

• Study drug related TEAEs causing discontinuation of study drug

[1045] Population summary measure of interest: For the endpoints looking only at the period defined by this study, the incidence and rate per 100 patient-years of each category of TEAEs. For the endpoints looking at the period defined by this study and the relevant parent study, the rate per 100 patient-years of each category of TEAEs by treatment group.

[1046] Strategies for intercurrent events:

• Discontinuation of treatment will use a composite strategy as the ‘treatment emergent’ includes the discontinuation of treatment as part of the definition

• The use of other medications (including permitted rescue therapies), non-compliance with study drug and any deviations from protocol will use a treatment policy strategy in which all data is used regardless of the intercurrent event

12.46.34. Secondary Efficacy Estimands

[1047] Population: The FAS will be used for all secondary estimands. Note that for interim analyses, a parent study specific analysis set may be used in place of the FAS.

[1048] Population summary measure of interest:

• For continuous endpoints, the mean at each scheduled visit will be used

• For responder endpoints, the percentage of participants with the relevant response will be used

• For rate endpoints, the number of events per patient-year will be used

[1049] Strategies for intercurrent events for continuous and response endpoint:

• Discontinuation of treatment: a treatment policy strategy will be followed in that there will be no window for days since discontinuation applied to exclude or change data. However, it should be noted that participants will be withdrawn from the study following discontinuation of treatment and as such it is expected that data collected at the scheduled visits will only include participants who are on treatment (or very recently discontinued) with the exception of those visits specifically scheduled to occur 4 and 12 weeks after last dose.

• Non-compliance with study drug and any deviations from protocol not relating to the use of other treatments for atopic dermatitis will use a treatment policy strategy in which all data is used regardless of the intercurrent event

• Use of rescue medications within 4 weeks and use at any time of other prohibited medications for atopic dermatitis will be considered using 3 separate strategies. The composite strategy will be used for all endpoints and in addition, supplementary estimands using the treatment policy strategy and the while on treatment strategy will be used for key secondary response endpoints (as indicated in Table 12-1: Secondary Efficacy Estimands)s o Treatment policy: including all data collected regardless of use of rescue medications or other prohibited medications for atopic dermatitis o While on treatment: excluding all data collected within 4 weeks after use of rescue medications or at any time after use of other prohibited medications for atopic dermatitis o Composite strategy: replacing data all data collected within 4 weeks after use of rescue medications or at any time after use of other prohibited medications for atopic dermatitis. Response endpoints will replace such data with ‘nonresponse’ and continuous endpoints will replace all data with the last observation carried forward. Note that observations will only be imputed for on-study timepoints, if a participant withdraws from the study before the relevant timepoint, the data will not be imputed for that timepoint but will be considered missing.

[1050] Strategies for intercurrent events for rate endpoints looking at rescue medication will use the same approach as specified for the primary estimands.

[1051] Endpoints: Table 11-1 shows the secondary efficacy endpoints defined for this study. All endpoints will be considered at all scheduled visits for response and continuous endpoints and will look at the rate over the course of the study and over the study combined with the relevant parent study.

Table 12-1: Secondary Efficacy Estimands

¹ For these endpoints, supplementary estimands will be shown using a) treatment policy and b) while on treatment strategies for the intercurrent events of use of rescue medication and/or prohibited medications in addition to the main secondary estimand which uses the composite strategy for these endpoints.

² Only for participants with relevant score > 2 or > 4 (as applicable) at baseline.

³ The score at each visit is calculated as the mean daily score for the 7 days prior to and including the visit date. At least 4 daily scores must be available for the score at the relevant visit to be considered evaluable.

12.46.35. Exploratory Estimands

[1052] Population: The FAS will be used for all exploratory efficacy estimands.

Note that for interim analyses, a parent study specific analysis set may be used in place of the FAS.

[1053] Details of the endpoints, population summary measures of interest and intercurrent event strategies can be found in Table 11-2.

Table 12-2: Exploratory Estimand Details

1 Only for participants with a non-zero baseline score in the relevant body region

12.46.36. Safety Estimands

[1054] All safety estimands (other than those already defined as primary) will use the FAS. A treatment policy approach will be used for all safety estimands, including all data collected regardless of treatment discontinuation, treatment compliance and use of other medications.

Table 12-3: Safety Estimand Details

12.47. Planned Analyses

[1055] All analyses will be descriptive in nature and no inferential statistics will be performed. 95% confidence intervals of mean changes and incidences or rates may be displayed where appropriate.

12.48. Handling of Protocol Deviations

[1056] Protocol deviations will be logged within the clinical trial management system and categorized dependent on the type of deviation and its significance.

Protocol deviations relating to the use of prohibited medications, and to non-compliance with study treatment (including non-compliant emollient use) before database lock will be accounted for as intercurrent events in the primary analysis.

12.49. Handling of Dropouts or Missing Data

[1057] Unless otherwise specified as part of the intercurrent event strategy, missing data will not be imputed.

[1058] Otherwise, missing data will not be imputed. 12.50. Planned Interim Analysis and Data Monitoring

[1059] Interim safety and efficacy analyses may be performed throughout the life cycle of the study as required for ongoing evaluation of the risk benefit profile for Prevotella histicola Strain B. These may include either all participants enrolled in the study or use a subset of participants who transitioned to this study from a specific parent study. Interim analyses will also incorporate data collected on the parent atopic dermatitis Prevotella histicola Strain B studies which feed into this study. At a minimum, there will be a parent-study specific analysis performed after all participants from each parent study have completed this study.

12.51. Determination of Sample Size

[1060] The sample size of the study will be determined by the number of participants who enroll from qualifying atopic dermatitis parent studies with Prevotella histicola Strain B.

13. ETHICS AND REGULATORY REQUIREMENTS

13.52. Informed Consent

[1061] Participant’s informed consent must be obtained and documented in accordance with local regulations, ICH-GCP requirements, and the ethical principles that have their origin in the principles of the Declaration of Helsinki.

13.53. Institutional Review Boards and Independent Ethics Committees

[1062] The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration of Helsinki.

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LIST OF ABBREVIATIONS

15. APPENDICES

15.1. Classification of Potency of Topical Corticosteroids

15.2. Contraceptive Guidance and Collection of Pregnancy Information

Definitions

Woman of Child-Bearing Potential (WOCBP)

[1063] A woman is considered fertile following menarche and until becoming postmenopausal unless permanently sterile (see below).

[1064] Women in the following categories are not considered WOCBP:

1. Premenarchal

2. Premenopausal female with 1 of the following:

• Documented hysterectomy

• Documented bilateral salpingectomy

• Documented bilateral oophorectomy [1065] Note: Documentation can come from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.

3. Postmenopausal female

• A postmenopausal state is defined as no menses for 12 months prior to the Day -1 Visit without an alternative medical cause. In the absence of 12 months of amenorrhea, postmenopausal women will be assumed to be WOCBP and will need to follow contraceptive guidance and have pregnancy tests performed throughout the course of the study per the Schedule of Activities (SOA).

• Females on HRT and whose menopausal status is in doubt will be required to use one of the non-estrogen hormonal highly effective contraception methods if they wish to continue their HRT during the study.

Contraception Guidance

Male participants with a female partner of child-bearing potential must either

• Be abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent

• Use a male condom during each episode of penile penetration during their participation in the study and for 90 days after the last dose of IMP.

• Have a confirmed vasectomy where the absence of sperm has been confirmed

[1066] In addition, all male participants must refrain from donating sperm for the duration of the study and for at least 90 days following their final visit.

Female participants

[1067] Female participants of child-bearing potential are eligible to participate if they agree to use a highly effective method of contraception consistently and correctly as described in the table below.

Table 15-1: Highly Effective Contraceptive Methods

Pregnancy Testing

• WOCBP should only be included after a confirmed menstrual period and a negative pregnancy test.

• Pregnancy testing is required at the Day -1 visit.

• Pregnancy testing will be performed whenever a menstrual cycle is missed or when pregnancy is otherwise suspected.

Collection of Pregnancy Information

[1068] Male participants with partners who become pregnant • The Investigator will attempt to collect pregnancy information on any male participant’s female partner who becomes pregnant while the male participant is in this study. This applies to all male participants who receive Prevotella histicola Strain B.

• After obtaining the necessary signed informed consent from the pregnant female partner directly, the Investigator will record pregnancy information on the appropriate form and submit it to the Sponsor within 24 hours of learning of the partner’s pregnancy. The female partner will also be followed to determine the outcome of the pregnancy. Information on the status of the mother and child will be forwarded to the Sponsor. Generally, the follow-up will be no longer than 8 weeks following the estimated delivery date. Any termination of the pregnancy will be reported regardless of foetal status (presence or absence of anomalies) or indication for the procedure.

[1069] Female participants who become pregnant

• The investigator will collect pregnancy information on any female participant who becomes pregnant while participating in this study. Information will be recorded on the appropriate form and submitted to the Sponsor within 24 hours of learning of a participant's pregnancy. The participant will be followed to determine the outcome of the pregnancy. The investigator will collect follow-up information on the participant and the neonate, and the information will be forwarded to the Sponsor. Generally, follow-up will not be required for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of pregnancy will be reported, regardless of foetal status (presence or absence of anomalies) or indication for the procedure.

• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is always considered to be an SAE and will be reported as such. Any post-study pregnancy related- SAE considered reasonably related to the study intervention by the Investigator will be reported to the Sponsor as described in Section 10.31 Reporting Serious Adverse Events. While the Investigator is not obligated to actively seek this information in former study participants, he or she may learn of an SAE through spontaneous reporting.

• Any female participant who becomes pregnant while participating in the study will discontinue study intervention or be withdrawn from the study. 15.3. Prevotella histicola Strain B COVID-19 Risk Assessment

[1070] Antiviral responses are activated rapidly after viral infection in order to control and prevent dissemination of the virus. Virus infection results in two general types of immune response. The first is a rapid onset innate immune response against the virus, which involves the synthesis of Type 1 interferons and the stimulation of Natural Killer (NK) cells. If the infection proceeds beyond the first few rounds of viral replication, the innate immune response will trigger the adaptive immune response. The adaptive immune response itself has two components, the humoral response (the synthesis of virus-specific antibodies by B lymphocytes) and the cell-mediated response (the synthesis of specific CD8+ cytotoxic T lymphocytes that kill infected cells). Both of these components of the adaptive immune response result in the production of long-lived memory cells that allow for a much more rapid response to a subsequent infection with the same virus. Thus, an immune competent host should be able to mount both an innate and adaptive immune response.

[1071] Prevotella histicola Strain B is a single strain of human commensal Prevotella histicola that is being clinically tested to treat inflammatory skin diseases such as psoriasis and atopic dermatitis; in a pharmacodynamic immune challenge study to Keyhole Limpet Haemocyanin (KLH); and also, to treat the complications of infection with COVID-19. Prevotella histicola Strain B is administered orally and is gut restricted. Therefore, Prevotella histicola Strain B exerts its anti-inflammatory effects on peripheral tissue through engagement of cells of the intestine, including small intestinal epithelial cells and immune cells in the lamina propria.

[1072] Prevotella histicola Strain B has been shown in preclinical mouse inflammation models to reduce antigen-specific T cell responses, without impacting:

• The anti-viral TLR3 -mediated Type 1 interferon (alpha and beta) response

• Interferon-gamma production by T cells and NK cells

• Immune cell subsets (absolute number and percentage), including CD8 T lymphocytes, B lymphocytes, and myeloid lineage cells

• The antigen-specific antibody responses (IgM and IgG)

[1073] In human immune cell in vitro assays, Prevotella histicola Strain B did not alter the ability of human dendritic cells to induce the production of interferon-gamma from memory CD8 T cells in response to a viral peptide pool (Cytomegalovirus, Epstein-Bar virus, and Influenza virus), an important component of an anti-viral response. [1074] And clinically, treatment with Prevotella histicola Strain B was shown to reduce specific inflammatory myeloid cell cytokines such as IL-6 and IL-8, while not affecting levels of T cell cytokines such as interferon-gamma, produced by circulating peripheral blood mononuclear cells.

[1075] Taken together, the data demonstrate that treatment with Prevotella histicola Strain B does not result in general immuno-suppression of multiple immune pathways but is effective through a selective restoration of immune homeostasis.

TLR3 -mediated induction of Type 1 interferons in the KLH delayed-type hypersensitivity model

[1076] Mice were immunized by subcutaneous injection with KLH emulsified with Complete Freund’s Adjuvant. On Day 6 after the sensitization, mice were dosed for 3 days with oral Prevotella histicola Strain B, or dexamethasone given intraperitoneally. On day 8, mice were challenged by intradermal ear injection with KLH. The DTH response was evaluated 24 hours post-challenge. For the ex vivo cytokine analysis, spleen cells from treated mice were incubated for 48 hours in vitro and stimulated with polyinosinic- polycytidylic acid (poly LC), a molecule that mimics viral double-strained RNA, and a potent ligand for Toll-like receptor 3, which induces interferon-alpha and interferon-beta from immune cells.

[1077] Results: Three days of dosing with Prevotella histicola Strain B or dexamethasone significantly inhibited ear inflammation. In addition, while dexamethasone significantly inhibited the production of interferon-alpha and interferon-beta in the spleen cell stimulation assay, oral Prevotella histicola Strain B had no impact on these Type 1 interferons. This demonstrates that Prevotella histicola Strain B selectively inhibits tissue inflammation while preserving protective Type 1 interferon responses.

Interferon-gamma production by lymphocytes in vivo

[1078] In the same study, spleen cells were restimulated with PMA and ionomycin. PMA activates protein kinase C, while ionomycin is a calcium ionophore, and stimulation with these compounds bypasses the T cell membrane receptor complex and will lead to activation of several intracellular signaling pathways, resulting in T cell activation and production of a variety of cytokines. Stimulation with PMA/ionomycin induced robust production of interferon-gamma from spleen cells, and treatment with Prevotella histicola Strain B or dexamethasone did not reduce the production of interferon-gamma, demonstrating that the Cytotoxic CD8 T cell/NK axis of immunity was intact. Immune cell subsets quantification after Prevotella histicola Strain B dosing

[1079] In other DTH studies, immune cell numbers in lymphoid tissues were measured. Mesenteric lymph nodes which drain the small intestine were removed at the end of a delayed-type hypersensitivity study, performed as described above. Single cell suspensions were made from the lymph nodes, stained using antibodies against cell surface markers, and quantified by flow cytometry. Treatment with Prevotella histicola Strain B for 5 days did not alter any immune cell subsets, including T cells, NK cells, B cells, neutrophils, macrophages, and monocytes in the lymph nodes.

KLH-specific antibody response

[1080] Antibodies are one of the essential features of antigen-triggered adaptive immunity against viruses and requires a coordinated response between antigen-presenting cells such as dendritic cells, antigen-specific helper T cells, and antigen-specific B cells. Although treatment with Prevotella histicola Strain B causes a marked reduction in peripheral inflammation in the KLH delayed-type hypersensitivity model, no effect on KLH-specific IgM or IgG has been observed in either preclinical models or in a clinical study (data not shown).

In vitro assay co-culture with human dendritic cells and CD8 T cells

[1081] An in vitro assay with primary human DCs and autologous CD8+ T cells was carried out to measure the capacity of Prevotella histicola Strain B to modulate antigen-specific CD8+ T cell responses. Briefly, primary human DCs from 3 healthy donors were differentiated in vitro for 7 days. To assess the immuno-modulatory properties of Prevotella histicola Strain B, DCs were incubated with Prevotella histicola Strain B, or with a different Prevotella strain that does not exhibit anti-inflammatory activity, for 24 hours in vitro. After 24 hours of microbe conditioning, microbes were removed from the DC culture and autologous human CD8+ T cells and CEF Class I peptide pool was added. The CEF peptide pool is composed of peptides from Cytomegalovirus, Epstein Bar virus, and Influenza virus, pathogens to which the majority of the human population has been exposed. After 24 hours of stimulation with CEF peptide, DC-CD8+ T cell supernatants were collected and IFNy was measured. When human DCs were incubated with Prevotella histicola Strain B, the IFNy response to CEF was not affected (neither enhanced nor decreased) compared to the DC-CD8 T cell co-culture control. In contrast, incubation with the different Prevotella strain led to increased production of IFNy. Conclusion

[1082] The combination of in vitro, in vivo, and ex vivo data demonstrate that Prevotella histicola Strain B does not broadly impair either innate or adaptive immune responses. Prevotella histicola Strain B is orally delivered and gut restricted, and therefore its effect is exerted through local interactions with cells of the small intestine, which are then translated from the gut to the periphery to resolve inflammation. Anti-viral responses such as cytotoxic T cell production of interferon-gamma, innate anti-viral production of interferon-alpha and interferon-beta, and the generation of high affinity antibodies are all preserved after treatment with Prevotella histicola Strain B.

[1083] The data demonstrate that treatment with Prevotella histicola Strain B results in resolution of multiple pathways of inflammation without leading to immunosuppression of the host response.

15.4. Toxicity Grading Scale

[1084] The following scales come from the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, September 2007.

Temperature Adverse Event Grading Scale

Laboratory Results Adverse Event Grading Scale

Incorporation by Reference

[1085] All publications patent applications mentioned herein are hereby incorporated by reference in their entirety as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. In case of conflict, the present application, including any definitions herein, will control.

Equivalents

[1086] Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

What is claimed is:

1. A method of treating a condition in a human subject comprising orally administering to the human subject a dose of about 1.6 x IO¹⁰ cells to about 16 x 10¹¹ cells of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks.

2. The method of claim 1, wherein the condition comprises psoriasis, optionally wherein the psoriasis is mild, moderate, or severe psoriasis.

3. The method of claim 1, wherein the condition comprises atopic dermatitis, optionally wherein the atopic dermatitis is mild, moderate, or severe atopic dermatitis.

4. The method of claim 1, wherein the condition comprises psoriatic arthritis, , optionally wherein the psoriasis is mild, moderate, or severe psoriatic arthritis.

5. The method of claim 1, wherein the condition comprises an inflammatory disease.

6. The method of claim 5, the inflammatory disease is a Thl, Th2, or Thl7 inflammatory disease.

7. The method of any one of claims 1 to 6, wherein the dose comprises about 8 x IO¹⁰ cells to about 8 x 10¹¹ cells.

8. The method of claim 7, wherein the dose comprises about 8 x IO¹⁰ cells.

9. The method of claim 7, wherein the dose comprises about 1.6 x 10¹¹ cells.

10. The method of claim 7, wherein the dose comprises about 6.4 x 10¹¹ cells.

11. The method of any one of claims 1 to 10, wherein the dose is administered to the subject once daily.

12. The method of any one of claims 1 to 10, wherein the dose is administered to the subject twice daily.

13. The method of any one of claims 1 to 12, wherein the dose is formulated in one or more solid dosage forms.

14. The method of claim 13, wherein the solid dosage form comprises about 8 x 10¹⁰ cells per solid dosage form.

15. The method of claim 13, wherein the solid dosage form comprises about 1.6 x 10¹¹ cells per solid dosage form.

16. The method of claim 13, wherein the solid dosage form comprises about 3.2 x 10¹¹ cells per solid dosage form.

17. The method of any one of claims 1 to 16, wherein the solid dosage form comprises a tablet or capsule.

18. The method of any one of claims 13 to 17, wherein the solid dosage form is enteric coated.

19. The method of any one of claims 13 to 18, wherein the one or more solid dosage forms are administered in combination with an additional therapy.

20. A method of treating psoriasis, optionally mild, moderate, or severe psoriasis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

21. A method of treating psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

22. A method of treating atopic dermatitis, optionally mild, moderate, or severe atopic dermatitis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage form is a tablet or a capsule.

23. A method of treating psoriasis, optionally mild, moderate, or severe psoriasis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

24. A method of treating psoriatic arthritis, optionally mild, moderate, or severe psoriatic arthritis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x IO¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

25. A method of treating atopic dermatitis, optionally mild, moderate, or severe atopic dermatitis, in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.

26. A method of treating inflammation in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in one solid dosage form, wherein the solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria , optionally wherein the solid dosage form is a tablet or a capsule.

27. A method of treating inflammation in a human subject comprising orally administering to the human subject a dose of Prevotella histicola Strain B 50329 (NRRL accession number B 50329) bacteria, wherein the dose is administered to the human subject for at least 20 weeks, wherein the dose is formulated in two solid dosage forms, wherein each solid dosage form comprises about 8 x 10¹⁰ total cells of the bacteria, optionally wherein the solid dosage forms are tablets or capsules.