Canhua Xiao1, Veronika Fedirko2, Jonathan Beitler3, Jinbing Bai4, Gang Peng5, Chao Zhou5, Jianlei Gu5, Hongyu Zhao5, I-Hsin Lin6, Cynthia E Chico7, Sangchoon Jeon8, Tish M Knobf8, Karen N Conneely9, Kristin Higgins3, Dong M Shin10, Nabil Saba10, Andrew Miller7, Deborah Bruner4. 1. School of Nursing, Yale University, 400 West Campus Drive, Room 20102, Orange, CT, 06477, USA. canhua.xiao@yale.edu. 2. School of Public Health, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA. 3. Department of Radiation, School of Medicine, Emory University, 1365-C Clifton Road NE, Atlanta, GA, 30322, USA. 4. School of Nursing, Emory University, 1520 Clifton Road NE, Atlanta, 30322, USA. 5. Department of Epidemiology and Public Health, School of Medicine, Yale University, 300 George Street, New Haven, CT, 06510, USA. 6. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, 485 Lexington Ave, New York, NY, 10017, USA. 7. Department of Psychiatry and Behavioral Sciences, School of Medicine, Emory University, 1365-B Clifton Road, Atlanta, GA, 30322, USA. 8. School of Nursing, Yale University, 400 West Campus Drive, Room 20102, Orange, CT, 06477, USA. 9. Department of Human Genetics, School of Medicine, Emory University, 201 Dowman Drive, Atlanta, GA, 30322, USA. 10. Department of Hematology and Medical Oncology, School of Medicine, Emory University, 1365-C Clifton Road NE, Atlanta, GA, 30322, USA.
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.
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.
Entities:
Keywords:
Cancer; Epigenetic changes; Fatigue; Gut microbiome
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