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The role of the gut microbiome in cancer-related fatigue: pilot study on epigenetic mechanisms

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Abstract

Purpose

Recent evidence supports a key role of gut microbiome in brain health. We conducted a pilot study to assess associations of gut microbiome with cancer-related fatigue and explore the associations with DNA methylation changes.

Methods

Self-reported Multidimensional Fatigue Inventory and stool samples were collected at pre-radiotherapy and one-month post-radiotherapy in patients with head and neck cancer. Gut microbiome data were obtained by sequencing the 16S ribosomal ribonucleic acid gene. DNA methylation changes in the blood were assessed using Illumina Methylation EPIC BeadChip.

Results

We observed significantly different gut microbiota patterns among patients with high vs. low fatigue across time. This pattern was characterized by low relative abundance in short-chain fatty acid–producing taxa (family Ruminococcaceae, genera Subdoligranulum and Faecalibacterium; all p < 0.05), with high abundance in taxa associated with inflammation (genera Family XIII AD3011 and Erysipelatoclostridium; all p < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (all p < 0.001), including pathways related to fatty acid synthesis and oxidation, inflammation, and brain function. Gene set enrichment analysis (GSEA) was performed on the top differentially methylated CpG sites that were associated with the taxa and fatigue. All biological processes from the GSEA were related to immune responses and inflammation (FDR < 0.05).

Conclusions

Our results suggest different patterns of the gut microbiota in cancer patients with high vs. low fatigue. Results from functional pathways and DNA methylation analyses indicate that inflammation is likely to be the major driver in the gut-brain axis for cancer-related fatigue.

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Funding

The study was support by NIH/NCI P30CA138292 and Yale University School of Nursing Pilot Grant.

Author information

Authors and Affiliations

  1. School of Nursing, Yale University, 400 West Campus Drive, Room 20102, Orange, CT, 06477, USA

    Canhua Xiao, Sangchoon Jeon & Tish M. Knobf

  2. School of Public Health, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA

    Veronika Fedirko

  3. Department of Radiation, School of Medicine, Emory University, 1365-C Clifton Road NE, Atlanta, GA, 30322, USA

    Jonathan Beitler & Kristin Higgins

  4. School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta, 30322, USA

    Jinbing Bai & Deborah Bruner

  5. Department of Epidemiology and Public Health, School of Medicine, Yale University, 300 George Street, New Haven, CT, 06510, USA

    Gang Peng, Chao Zhou, Jianlei Gu & Hongyu Zhao

  6. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 485 Lexington Ave, New York, NY, 10017, USA

    I-Hsin Lin

  7. Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA, 30322, USA

    Cynthia E. Chico & Andrew Miller

  8. Department of Human Genetics, School of Medicine, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA

    Karen N. Conneely

  9. Department of Hematology and Medical Oncology, School of Medicine, Emory University, 1365-C Clifton Road NE, Atlanta, GA, 30322, USA

    Dong M. Shin & Nabil Saba

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  1. Canhua Xiao
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  2. Veronika Fedirko
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  9. I-Hsin Lin
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  15. Dong M. Shin
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Correspondence to Canhua Xiao.

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Xiao, C., Fedirko, V., Beitler, J. et al. The role of the gut microbiome in cancer-related fatigue: pilot study on epigenetic mechanisms. Support Care Cancer 29, 3173–3182 (2021). https://doi.org/10.1007/s00520-020-05820-3

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  • DOI: https://doi.org/10.1007/s00520-020-05820-3

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