• Support Care Cancer · Jun 2021

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

    • Canhua Xiao, Veronika Fedirko, Jonathan Beitler, Jinbing Bai, Gang Peng, Chao Zhou, Jianlei Gu, Hongyu Zhao, I-Hsin Lin, Cynthia E Chico, Sangchoon Jeon, Tish M Knobf, Karen N Conneely, Kristin Higgins, Dong M Shin, Nabil Saba, Andrew Miller, and Deborah Bruner.
    • School of Nursing, Yale University, 400 West Campus Drive, Room 20102, Orange, CT, 06477, USA. canhua.xiao@yale.edu.
    • Support Care Cancer. 2021 Jun 1; 29 (6): 3173-3182.

    PurposeRecent 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.MethodsSelf-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.ResultsWe 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).ConclusionsOur 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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