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

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, generaSubdoligranulumandFaecalibacterium; allp < 0.05), with high abundance in taxa associated with inflammation (generaFamily XIII AD3011andErysipelatoclostridium; allp < 0.05) for high-fatigue group. We identified nine KEGG Orthology pathways significantly different between high- vs. low-fatigue groups over time (allp < 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.

Automated summary

Our study identified significantly different gut microbiota patterns in cancer patients with high vs. low fatigue, characterized by inflammation-associated taxa in high-fatigue group. Functional pathways and DNA methylation analyses indicate inflammation as the major driver in the gut-brain axis for cancer-related fatigue.