Abstract
The intestinal microbiome is a signalling hub that integrates environmental inputs, such as diet, with genetic and immune signals to affect the host's metabolism, immunity and response to infection. The haematopoietic and non-haematopoietic cells of the innate immune system are located strategically at the host–microbiome interface. These cells have the ability to sense microorganisms or their metabolic products and to translate the signals into host physiological responses and the regulation of microbial ecology. Aberrations in the communication between the innate immune system and the gut microbiota might contribute to complex diseases.
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References
Thaiss, C. A., Levy, M., Itav, S. & Elinav, E. Integration of innate immune signaling. Trends Immunol. 37, 84–101 (2016).
Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).
Shibolet, O. & Podolsky, D. K. TLRs in the gut. IV. Negative regulation of Toll-like receptors and intestinal homeostasis: addition by subtraction. Am. J. Physiol. Gastrointest. Liver Physiol. 292, G1469–G1473 (2007).
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S. & Medzhitov, R. Recognition of commensal microflora by Toll-like receptors is required for intestinal homeostasis. Cell 118, 229–241 (2004). Refs 4 and 5 highlight the importance of innate-immune-system recognition of the microbiota for host–microbiota homeostasis.
Slack, E. et al. Innate and adaptive immunity cooperate flexibly to maintain host–microbiota mutualism. Science 325, 617–620 (2009).
Pfeiffer, J. K. & Virgin, H. W. Transkingdom control of viral infection and immunity in the mammalian intestine. Science 351, aad5872 (2016).
Underhill, D. M. & Pearlman, E. Immune interactions with pathogenic and commensal fungi: a two-way street. Immunity 43, 845–858 (2015).
Thaiss, C. A., Levy, M., Suez, J. & Elinav, E. The interplay between the innate immune system and the microbiota. Curr. Opin. Immunol. 26, 41–48 (2014).
Pott, J. & Hornef, M. Innate immune signalling at the intestinal epithelium in homeostasis and disease. EMBO Rep. 13, 684–698 (2012).
Nenci, A. et al. Epithelial NEMO links innate immunity to chronic intestinal inflammation. Nature 446, 557–561 (2007).
Vaishnava, S. et al. The antibacterial lectin RegIIIγ promotes the spatial segregation of microbiota and host in the intestine. Science 334, 255–258 (2011).
Vlantis, K. et al. TLR-independent anti-inflammatory function of intestinal epithelial TRAF6 signalling prevents DSS-induced colitis in mice. Gut http://dx.doi.org/10.1136/gutjnl-2014-308323 (2015).
Dannappel, M. et al. RIPK1 maintains epithelial homeostasis by inhibiting apoptosis and necroptosis. Nature 513, 90–94 (2014).
Günther, C. et al. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis. Nature 477, 335–339 (2011).
Takahashi, N. et al. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis. Nature 513, 95–99 (2014).
Welz, P.-S. et al. FADD prevents RIP3-mediated epithelial cell necrosis and chronic intestinal inflammation. Nature 477, 330–334 (2011).
Couturier-Maillard, A. et al. NOD2-mediated dysbiosis predisposes mice to transmissible colitis and colorectal cancer. J. Clin. Invest. 123, 700–711 (2013).
Nigro, G., Rossi, R., Commere, P. H., Jay, P. & Sansonetti, P. J. The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15, 792–798 (2014).
Ramanan, D., Tang, M. S., Bowcutt, R., Loke, P. & Cadwell, K. Bacterial sensor Nod2 prevents inflammation of the small intestine by restricting the expansion of the commensal Bacteroides vulgatus. Immunity 41, 311–324 (2014).
Bouskra, D. et al. Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 456, 507–510 (2008).
Nordlander, S., Pott, J. & Maloy, K. J. NLRC4 expression in intestinal epithelial cells mediates protection against an enteric pathogen. Mucosal Immunol. 7, 775–785 (2014).
Sellin, M. E. et al. Epithelium-intrinsic NAIP/NLRC4 inflammasome drives infected enterocyte expulsion to restrict Salmonella replication in the intestinal mucosa. Cell Host Microbe 16, 237–248 (2014).
Allam, R. et al. Epithelial NAIPs protect against colonic tumorigenesis. J. Exp. Med. 212, 369–383 (2015).
Hu, B. et al. Inflammation-induced tumorigenesis in the colon is regulated by caspase-1 and NLRC4. Proc. Natl Acad. Sci. USA 107, 21635–21640 (2010).
Levy, M. et al. Microbiota-modulated metabolites shape the intestinal microenvironment by regulating NLRP6 inflammasome signaling. Cell 163, 1428–1443 (2015). Refs 25–29 demonstrate the role of epithelial NLRP6 in orchestrating antimicrobial peptide production, mucus secretion and viral recognition.
Wlodarska, M. et al. NLRP6 inflammasome orchestrates the colonic host–microbial interface by regulating goblet cell mucus secretion. Cell 156, 1045–1059 (2014).
Elinav, E. et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 145, 745–757 (2011).
Normand, S. et al. Nod-like receptor pyrin domain-containing protein 6 (NLRP6) controls epithelial self-renewal and colorectal carcinogenesis upon injury. Proc. Natl Acad. Sci. USA 108, 9601–9606 (2011).
Wang, P. et al. Nlrp6 regulates intestinal antiviral innate immunity. Science 350, 826–830 (2015).
Macia, L. et al. Metabolite-sensing receptors GPR43 and GPR109A facilitate dietary fibre-induced gut homeostasis through regulation of the inflammasome. Nature Commun. 6, 6734 (2015).
Singh, N. et al. Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40, 128–139 (2014).
Hu, S. et al. The DNA sensor AIM2 maintains intestinal homeostasis via regulation of epithelial antimicrobial host defense. Cell Rep. 13, 1922–1936 (2015).
Man, S. M. et al. Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell 162, 45–58 (2015).
Song-Zhao, G. X. et al. Nlrp3 activation in the intestinal epithelium protects against a mucosal pathogen. Mucosal Immunol. 7, 763–774 (2014).
Kelly, C. J. et al. Crosstalk between microbiota-derived short-chain fatty acids and intestinal epithelial HIF augments tissue barrier function. Cell Host Microbe 17, 662–671 (2015).
Venkatesh, M. et al. Symbiotic bacterial metabolites regulate gastrointestinal barrier function via the xenobiotic sensor PXR and Toll-like receptor 4. Immunity 41, 296–310 (2014).
Chimerel, C. et al. Bacterial metabolite indole modulates incretin secretion from intestinal enteroendocrine L cells. Cell Rep. 9, 1202–1208, (2014).
Mukherji, A., Kobiita, A., Ye, T. & Chambon, P. Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs. Cell 153, 812–827 (2013).
Thaiss, C. A. & Elinav, E. Exploring new horizons in microbiome research. Cell Host Microbe 15, 662–667 (2014).
Zarrinpar, A., Chaix, A., Yooseph, S. & Panda, S. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Cell Metab. 20, 1006–1017 (2014).
Khosravi, A. et al. Gut microbiota promote hematopoiesis to control bacterial infection. Cell Host Microbe 15, 374–381 (2014).
Balmer, M. L. et al. Microbiota-derived compounds drive steady-state granulopoiesis via MyD88/TICAM signaling. J. Immunol. 193, 5273–5283 (2014).
Trompette, A. et al. Gut microbiota metabolism of dietary fiber influences allergic airway disease and hematopoiesis. Nature Med. 20, 159–166 (2014).
Deshmukh, H. S. et al. The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice. Nature Med. 20, 524–530 (2014).
Gomez de Agüero, M. et al. The maternal microbiota drives early postnatal innate immune development. Science 351, 1296–1302 (2016).
Zhang, D. et al. Neutrophil ageing is regulated by the microbiome. Nature 525, 528–532 (2015).
Hill, D. A. et al. Commensal bacteria-derived signals regulate basophil hematopoiesis and allergic inflammation. Nature Med. 18, 538–546 (2012).
Erny, D. et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nature Neurosci. 18, 965–977 (2015).
Tamoutounour, S. et al. Origins and functional specialization of macrophages and of conventional and monocyte-derived dendritic cells in mouse skin. Immunity 39, 925–938 (2013).
Kim, Y. G. et al. Gut dysbiosis promotes M2 macrophage polarization and allergic airway inflammation via fungi-induced PGE2. Cell Host Microbe 15, 95–102 (2014).
Chang, P. V., Hao, L., Offermanns, S. & Medzhitov, R. The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proc. Natl Acad. Sci. USA 111, 2247–2252 (2014).
Bain, C. C. et al. Constant replenishment from circulating monocytes maintains the macrophage pool in the intestine of adult mice. Nature Immunol. 15, 929–937 (2014).
Muller, P. A. et al. Crosstalk between muscularis macrophages and enteric neurons regulates gastrointestinal motility. Cell 158, 300–313 (2014); erratum 158, 1210 (2014).
Fonseca, D. M. et al. Microbiota-dependent sequelae of acute infection compromise tissue-specific immunity. Cell 163, 354–366 (2015).
Ganal, S. C. et al. Priming of natural killer cells by nonmucosal mononuclear phagocytes requires instructive signals from commensal microbiota. Immunity 37, 171–186 (2012).
Schwab, L. et al. Neutrophil granulocytes recruited upon translocation of intestinal bacteria enhance graft-versus-host disease via tissue damage. Nature Med. 20, 648–654 (2014).
Oh, J. Z. et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41, 478–492 (2014).
Iida, N. et al. Commensal bacteria control cancer response to therapy by modulating the tumor microenvironment. Science 342, 967–970 (2013).
Sawa, S. et al. Lineage relationship analysis of RORγt+ innate lymphoid cells. Science 330, 665–669 (2010).
Sanos, S. L. et al. RORγt and commensal microflora are required for the differentiation of mucosal interleukin 22-producing NKp46+ cells. Nature Immunol. 10, 83–91 (2009).
Satoh-Takayama, N. et al. Microbial flora drives interleukin 22 production in intestinal NKp46+ cells that provide innate mucosal immune defense. Immunity 29, 958–970 (2008).
Sawa, S. et al. RORγt+ innate lymphoid cells regulate intestinal homeostasis by integrating negative signals from the symbiotic microbiota. Nature Immunol. 12, 320–326 (2011).
Sonnenberg, G. F. et al. Innate lymphoid cells promote anatomical containment of lymphoid-resident commensal bacteria. Science 336, 1321–1325 (2012). Refs 63–65 demonstrate a role for innate lymphoid cells in the local containment of the microbiota and in regulating T-cell responses to the microbiota.
Hepworth, M. R. et al. Innate lymphoid cells regulate CD4+ T-cell responses to intestinal commensal bacteria. Nature 498, 113–117 (2013).
Hepworth, M. R. et al. Group 3 innate lymphoid cells mediate intestinal selection of commensal bacteria-specific CD4+ T cells. Science 348, 1031–1035 (2015).
Mortha, A. et al. Microbiota-dependent crosstalk between macrophages and ILC3 promotes intestinal homeostasis. Science 343, 1249288 (2014).
Kinnebrew, M. A. et al. Interleukin 23 production by intestinal CD103+CD11b+ dendritic cells in response to bacterial flagellin enhances mucosal innate immune defense. Immunity 36, 276–287 (2012).
Kruglov, A. A. et al. Nonredundant function of soluble LTα3 produced by innate lymphoid cells in intestinal homeostasis. Science 342, 1243–1246 (2013).
Goto, Y. et al. Innate lymphoid cells regulate intestinal epithelial cell glycosylation. Science 345, 1254009 (2014).
Sonnenberg, G. F. & Artis, D. Innate lymphoid cell interactions with microbiota: implications for intestinal health and disease. Immunity 37, 601–610 (2012).
von Moltke, J., Ji, M., Liang, H. E. & Locksley, R. M. Tuft-cell-derived IL-25 regulates an intestinal ILC2-epithelial response circuit. Nature 529, 221–225 (2016).
Powell, N. et al. The transcription factor T-bet regulates intestinal inflammation mediated by interleukin-7 receptor+ innate lymphoid cells. Immunity 37, 674–684 (2012).
Levy, M., Thaiss, C. A. & Elinav, E. Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome. Genome Med. 7, 120 (2015).
Petnicki-Ocwieja, T. et al. Nod2 is required for the regulation of commensal microbiota in the intestine. Proc. Natl Acad. Sci. USA 106, 15813–15818 (2009).
Vijay-Kumar, M. et al. Metabolic syndrome and altered gut microbiota in mice lacking Toll-like receptor 5. Science 328, 228–231 (2010).
Pickard, J. M. et al. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. Nature 514, 638–641 (2014).
Kamdar, K. et al. Genetic and metabolic signals during acute enteric bacterial infection alter the microbiota and drive progression to chronic inflammatory disease. Cell Host Microbe 19, 21–31 (2016).
Ubeda, C. et al. Familial transmission rather than defective innate immunity shapes the distinct intestinal microbiota of TLR-deficient mice. J. Exp. Med. 209, 1445–1456 (2012).
Hooper, L. V. et al. Molecular analysis of commensal host-microbial relationships in the intestine. Science 291, 881–884 (2001). This study provided initial insight into the effects of commensal bacteria on genome-wide transcriptional reprogramming.
Kernbauer, E., Ding, Y. & Cadwell, K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 516, 94–98 (2014).
Rakoff-Nahoum, S. et al. Analysis of gene-environment interactions in postnatal development of the mammalian intestine. Proc. Natl Acad. Sci. USA 112, 1929–1936 (2015).
Sommer, F., Nookaew, I., Sommer, N., Fogelstrand, P. & Backhed, F. Site-specific programming of the host epithelial transcriptome by the gut microbiota. Genome Biol. 16, 62 (2015).
Leone, V. et al. Effects of diurnal variation of gut microbes and high-fat feeding on host circadian clock function and metabolism. Cell Host Microbe 17, 681–689 (2015).
Rawls, J. F., Mahowald, M. A., Ley, R. E. & Gordon, J. I. Reciprocal gut microbiota transplants from zebrafish and mice to germ-free recipients reveal host habitat selection. Cell 127, 423–433 (2006).
Chung, H. et al. Gut immune maturation depends on colonization with a host-specific microbiota. Cell 149, 1578–1593 (2012).
Patrick, S. et al. A unique homologue of the eukaryotic protein-modifier ubiquitin present in the bacterium Bacteroides fragilis, a predominant resident of the human gastrointestinal tract. Microbiology 157, 3071–3078 (2011).
Neish, A. S. et al. Prokaryotic regulation of epithelial responses by inhibition of IκB-α ubiquitination. Science 289, 1560–1563 (2000).
Kumar, A. et al. Commensal bacteria modulate cullin-dependent signaling via generation of reactive oxygen species. EMBO J. 26, 4457–4466 (2007).
Kelly, D. et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-γ and RelA. Nature Immunol. 5, 104–112 (2004).
Zhang, Q. et al. Commensal bacteria direct selective cargo sorting to promote symbiosis. Nature Immunol. 16, 918–926 (2015).
Camp, J. G. et al. Microbiota modulate transcription in the intestinal epithelium without remodeling the accessible chromatin landscape. Genome Res. 24, 1504–1516 (2014).
Takahashi, K. et al. Epigenetic control of the host gene by commensal bacteria in large intestinal epithelial cells. J. Biol. Chem. 286, 35755–35762 (2011).
Olszak, T. et al. Microbial exposure during early life has persistent effects on natural killer T cell function. Science 336, 489–493 (2012).
Alenghat, T. et al. Histone deacetylase 3 coordinates commensal-bacteria-dependent intestinal homeostasis. Nature 504, 153–157 (2013).
Chen, G. Y., Liu, M., Wang, F., Bertin, J. & Nunez, G. A functional role for Nlrp6 in intestinal inflammation and tumorigenesis. J. Immunol. 186, 7187–7194 (2011).
Jiang, W. et al. Recognition of gut microbiota by NOD2 is essential for the homeostasis of intestinal intraepithelial lymphocytes. J. Exp. Med. 210, 2465–2476 (2013).
Kobayashi, K. S. et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science 307, 731–734 (2005).
Franchi, L. et al. NLRC4-driven production of IL-1β discriminates between pathogenic and commensal bacteria and promotes host intestinal defense. Nature Immunol. 13, 449–456 (2012).
Zheng, Y. et al. Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nature Med. 14, 282–289 (2008).
Diehl, G. E. et al. Microbiota restricts trafficking of bacteria to mesenteric lymph nodes by CX3CR1hi cells. Nature 494, 116–120 (2013).
Macpherson, A. J. & Uhr, T. Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science 303, 1662–1665 (2004). This seminal study defined the lymph-node-restricted 'firewall' circuits that control the local containment of the microbiota.
Sano, T. et al. An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local effector Th17 responses. Cell 163, 381–393 (2015).
Naik, S. et al. Commensal–dendritic-cell interaction specifies a unique protective skin immune signature. Nature 520, 104–108 (2015).
Balmer, M. L. et al. The liver may act as a firewall mediating mutualism between the host and its gut commensal microbiota. Sci. Transl. Med. 6, 237ra66 (2014).
Zeissig, S. & Blumberg, R. S. Life at the beginning: perturbation of the microbiota by antibiotics in early life and its role in health and disease. Nature Immunol. 15, 307–310 (2014).
Henao-Mejia, J. et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 482, 179–185 (2012).
Luo, Y. et al. Microbiota from obese mice regulate hematopoietic stem cell differentiation by altering the bone niche. Cell Metab. 22, 886–894 (2015).
Abt, M. C. et al. Commensal bacteria calibrate the activation threshold of innate antiviral immunity. Immunity 37, 158–170 (2012).
Ichinohe, T. et al. Microbiota regulates immune defense against respiratory tract influenza A virus infection. Proc. Natl Acad. Sci. USA 108, 5354–5359 (2011).
Nice, T. J. et al. Interferon-λ cures persistent murine norovirus infection in the absence of adaptive immunity. Science 347, 269–273 (2015).
Zhang, B. et al. Prevention and cure of rotavirus infection via TLR5/NLRC4-mediated production of IL-22 and IL-18. Science 346, 861–865 (2014).
Hernández, P. P. et al. Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection. Nature Immunol. 16, 698–707 (2015).
Baldridge, M. T. et al. Commensal microbes and interferon-λ determine persistence of enteric murine norovirus infection. Science 347, 266–269 (2015).
Kane, M. et al. Successful transmission of a retrovirus depends on the commensal microbiota. Science 334, 245–249 (2011).
Kuss, S. K. et al. Intestinal microbiota promote enteric virus replication and systemic pathogenesis. Science 334, 249–252 (2011).
Guo, X. et al. Innate lymphoid cells control early colonization resistance against intestinal pathogens through ID2-dependent regulation of the microbiota. Immunity 42, 731–743 (2015).
Kamada, N. et al. Regulated virulence controls the ability of a pathogen to compete with the gut microbiota. Science 336, 1325–1329 (2012).
Behnsen, J. et al. The cytokine IL-22 promotes pathogen colonization by suppressing related commensal bacteria. Immunity 40, 262–273 (2014).
Maekawa, T. et al. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe 15, 768–778 (2014).
Carvalho, F. A. et al. Transient inability to manage proteobacteria promotes chronic gut inflammation in TLR5-deficient mice. Cell Host Microbe 12, 139–152 (2012).
Rigottier-Gois, L. Dysbiosis in inflammatory bowel diseases: the oxygen hypothesis. ISME J. 7, 1256–1261 (2013).
Hugot, J. P. et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 411, 599–603 (2001).
Ogura, Y. et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature 411, 603–606 (2001).
Hampe, J. et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nature Genet. 39, 207–211 (2007).
Rioux, J. D. et al. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nature Genet. 39, 596–604 (2007).
Iliev, I. D. et al. Interactions between commensal fungi and the C-type lectin receptor Dectin-1 influence colitis. Science 336, 1314–1317 (2012).
Kostic, A. D. et al. The dynamics of the human infant gut microbiome in development and in progression toward type 1 diabetes. Cell Host Microbe 17, 260–273 (2015).
Wen, L. et al. Innate immunity and intestinal microbiota in the development of type 1 diabetes. Nature 455, 1109–1113 (2008).
Scher, J. U. et al. Expansion of intestinal Prevotella copri correlates with enhanced susceptibility to arthritis. eLife 2, e01202 (2013).
Stefka, A. T. et al. Commensal bacteria protect against food allergen sensitization. Proc. Natl Acad. Sci. USA 111, 13145–13150 (2014).
Ji, Y. et al. Diet-induced alterations in gut microflora contribute to lethal pulmonary damage in TLR2/TLR4-deficient mice. Cell Rep. 8, 137–149 (2014).
Donath, M. Y. & Shoelson, S. E. Type 2 diabetes as an inflammatory disease. Nature Rev. Immunol. 11, 98–107 (2011).
Turnbaugh, P. J. et al. An obesity-associated gut microbiome with increased capacity for energy harvest. Nature 444, 1027–1031 (2006). One of the first studies to link dysbiosis to disease.
Wang, X. et al. Interleukin-22 alleviates metabolic disorders and restores mucosal immunity in diabetes. Nature 514, 237–241 (2014).
Le Chatelier, E. et al. Richness of human gut microbiome correlates with metabolic markers. Nature 500, 541–546 (2013).
Yang, T. et al. Gut dysbiosis is linked to hypertension. Hypertension 65, 1331–1340 (2015).
Rune, I. et al. Modulating the gut microbiota improves glucose tolerance, lipoprotein profile and atherosclerotic plaque development in ApoE-deficient mice. PLoS ONE 11, e0146439 (2016).
Koren, O. et al. Human oral, gut, and plaque microbiota in patients with atherosclerosis. Proc. Natl Acad. Sci. USA 108 (suppl.), 4592–4598 (2011).
Koeth, R. A. et al. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nature Med. 19, 576–585 (2013). Refs 139–141 explore the causative involvement of specific bacterial metabolites in metabolic disease.
Wang, Z. et al. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature 472, 57–63 (2011).
Wang, Z. et al. Non-lethal inhibition of gut microbial trimethylamine production for the treatment of atherosclerosis. Cell 163, 1585–1595 (2015).
Jin, C., Henao-Mejia, J. & Flavell, R. A. Innate immune receptors: key regulators of metabolic disease progression. Cell Metab. 17, 873–882 (2013).
Irrazábal, T., Belcheva, A., Girardin, S. E., Martin, A. & Philpott, D. J. The multifaceted role of the intestinal microbiota in colon cancer. Mol. Cell 54, 309–320 (2014).
Grivennikov, S. I. et al. Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth. Nature 491, 254–258 (2012).
Sivan, A. et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350, 1084–1089 (2015).
Ahern, P. P., Faith, J. J. & Gordon, J. I. Mining the human gut microbiota for effector strains that shape the immune system. Immunity 40, 815–823 (2014).
Zmora, N., Zeevi, D., Korem, T., Segal, E. & Elinav, E. Taking it personally: personalized utilization of the human microbiome in health and disease. Cell Host Microbe 19, 12–20 (2016).
Acknowledgements
We apologize to those authors whose relevant work could not be included owing to space constraints. We thank the members of the Elinav laboratory for discussions. C.A.T. received a Boehringer Ingelheim Fonds PhD fellowship. N.Z. is supported by the Gilead Sciences International Research Scholars Program in Liver Disease. E.E. is supported by: Y. and R. Ungar; the Abisch Frenkel Foundation for the Promotion of Life Sciences; the Gurwin Family Fund for Scientific Research; the Leona M. and Harry B. Helmsley Charitable Trust; the Crown Endowment Fund for Immunological Research; the estate of J. Gitlitz; the estate of L. Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; the Adelis Foundation; J. L. and V. Schwartz; A. and G. Markovitz; A. and C. Adelson; the French National Center for Scientific Research (CNRS); D. L. Schwarz; the V. R. Schwartz Research Fellow Chair; L. Steinberg; J. N. Halpern; A. Edelheit; grants funded by the European Research Council; a Marie Curie Career Integration Grant; the German–Israeli Foundation for Scientific Research and Development; the Israel Science Foundation; the Minerva Foundation; the Rising Tide Foundation; the Helmholtz Association; and the European Foundation for the Study of Diabetes. E.E. is the incumbent of the Rina Gudinski Career Development Chair.
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Thaiss, C., Zmora, N., Levy, M. et al. The microbiome and innate immunity. Nature 535, 65–74 (2016). https://doi.org/10.1038/nature18847
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DOI: https://doi.org/10.1038/nature18847
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