Abstract
Objectives The objectives of this proof of concept study were to (a) examine the temporal changes in fatigue and diversity of the gut microbiome over the course of chemoradiotherapy (CRT) in adults with rectal cancers; (b) investigate whether there are differences in diversity of the gut microbiome between fatigued and nonfatigued participants at the middle and at the end of CRT; and (c) investigate whether there are differences in the relative abundance of fecal microbiota at the phylum and genus levels between fatigued and nonfatigued participants at the middle and at the end of CRT. Methods Stool samples and symptom ratings were collected prior to the inception of CRT, at the middle (after 12–16 treatments) and at the end (after 24–28 treatments) of the CRT. Descriptive statistics and Mann–Whitney U test were computed for fatigue. Gut microbiome data were analyzed using the QIIME2 software. Results Participants (N = 29) ranged in age from 37 to 80 years. The median fatigue score significantly changed at the end of CRT (median = 23.0) compared with the median score before the initiation of CRT for the total sample (median = 17.0; p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, t(23) = 2.08, p ≤ 0.05). At the middle of CRT, the alpha diversity (abundance of Operational Taxonomic Units) was lower for fatigued participants (149.30 ± 53.1) than for nonfatigued participants (189.15 ± 44.18, Proteobacteria, Firmicutes, and Bacteroidetes were the dominant phyla for fatigued participants, and Escherichia, Bacteroides, Faecalibacterium, and Oscillospira were the most abundant genera for fatigued participants. Conclusion CRT-associated perturbation of the gut microbiome composition may contribute to fatigue.
Highlights
Advanced rectal cancer (RC) is treated with concomitant chemotherapy and radiation therapy (CRT) with curative intent [1]
Advances in Medicine effects such as fatigue with negative impacts on health-related quality of life [2]. e etiology and associated mechanism of the cancer-related fatigue during CRT treatment remain elusive [3]. ere is some evidence, that suggests that cancer treatment-induced gut microbial perturbation/dysbiosis contributes to inflammation-enabling translocation of bacteria and microbially-mediated metabolites into systemic circulation and inducing aberrant activation of the immune system such as cytokine-induced inflammatory reaction, which can affect brain function and induce behavioral symptoms such as fatigue [4,5,6,7,8]
We demonstrated that at the middle of treatment, the majority of bacteria present in the gut of nonfatigued participants was represented by two distinct phyla: the Verrucomicrobia phylum (Akkermansia genus, a beneficial microbe) and the Firmicutes phylum (Ruminococcus genera and Oscillospira genera). is is important given that Akkermansia has been reported to lead to anti-inflammatory action in the intestinal tract and the enhancement of the intestinal barrier function [41]
Summary
Advanced rectal cancer (RC) is treated with concomitant chemotherapy and radiation therapy (CRT) with curative intent [1]. Standard radiation therapy oncology group (RTOG) fields are used, which encompass the rectum, regional nodes, and pelvic small bowel. E etiology and associated mechanism of the cancer-related fatigue during CRT treatment remain elusive [3]. Not enough microbiomic studies exist to identify associations between changes of the gut microbiota and fatigue severity during CRT for RC. Fatigue phenotyping focused on gut microbiome perturbation can be a first step towards a better understanding of the biology of CRT-associated fatigue and the development of personalized medicine/interventions to target phenotype-based characteristics
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