Association of Radiotherapy-Related Intestinal Injury and Cancer-related Fatigue: A Brief Review and Commentary.

Radiotherapy treatment-induced intestinal injury and gut microbial perturbation/dysbiosis have been implicated in the pathobiology of cancer-related fatigue. The objective of this brief review was to explore the available evidence of the relationship between intestinal injury and self-reported fatigue, especially among cancer patients. The scientific evidence-including our own-linking gut mucosal barrier dysfunction and gut microbial perturbation/dysbiosis induced by cancer treatment with worsening of cancer related fatigue (perhaps through the gut-brain axis) is limited but promising. Emerging data suggest that lifestyle interventions and the administration of specific probiotics may favorably modulate the gut microbiota and potentially mediate beneficial effects leading to improvements in fatigue.

Gut microbiota and fatigue in rectal cancer patients: a cross-sectional pilot study.

CONTEXT: Although microbial-mediated disturbance of intestinal mucosal homeostasis (dysbiosis) is believed to contribute to the pathogenesis of chemotherapy and radiotherapy (CRT)-related fatigue, potential differences in the gut microbial diversity and in the abundance of gut microbial taxa between fatigued and non-fatigued patients have not been adequately examined, particularly in the rectal cancer population. PURPOSE: In this cross-sectional study, we aim to examine the differences in (a) gut microbial diversity and gut microbial abundances and (b) predicted functional pathways of the gut microbiome between rectal cancer participants with and without fatigue at the end of CRT. METHODS: Rectal cancer patients (n = 50) provided stool samples for 16S rRNA gene sequencing and symptom ratings for fatigue at the end of CRT. Gut microbiome data were analyzed using QIIME2, LEfSe, and the R statistical package. RESULTS: Fatigued (n = 35) participants showed enriched bacterial abundances of Eubacterium, Streptococcus, Adlercreutzia, and Actinomyces, as well as enriched abundances of the microbial sucrose degradation pathway, compared to non-fatigued patients at the end of CRT (n = 15). CONCLUSIONS: Differentially abundant microbial taxa were identified in fatigued and non-fatigued rectal cancer participants at the end of CRT. However, the exact role of these taxa (and identification of species) in the biology of CRT-related fatigue remains to be examined.

The Role of Gut Microbiome Perturbation in Fatigue Induced by Repeated Stress from Chemoradiotherapy: A Proof of Concept Study.

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.

Factors Affecting the Severity of Fatigue during Radiotherapy for Prostate Cancer; an Exploratory Study.

INTRODUCTION: Limited studies have examined potential risk factors associated with the fatigue experience of a sample of Puerto Rican men treated with radiotherapy for non-metastatic prostate cancer. Identifying these factors may provide initial information about targets for individualized interventions, leading to more effective management of fatigue in this population. PURPOSE: To examine the relationship of age, body max index, depressive symptoms, physical activity, and sleep disturbance with fatigue during radiotherapy for prostate cancer. METHODS: Twenty six participants completed five inventories: demographic intake, health form, the Functional Assessment of Cancer-Therapy-fatigue, Patient-Reported Outcome Measures Information System-Sleep disturbance, and the International Physical Activity Questionnaire-Short Form before, middle/days 19-21 and completion/days 38-42 of radiotherapy. The principal investigator rated the Hamilton depression scale. Descriptive statistics were performed. Interactions and influence of variables on fatigue were assessed using bivariate correlation and multiple linear regression, respectively. RESULTS: At each study time point, sleep disturbance and depressive symptoms were strongly correlated with each other and fatigue. The linear combination of sleep disturbance and depressive symptoms was significantly related to fatigue. CONCLUSION: Given the high association of sleep disturbance and depressive symptoms with fatigue, clinicians should assess and develop interventions to manage these symptoms altogether.

Gut microbiota perturbation is associated with acute sleep disturbance among rectal cancer patients.

Cancer treatment-associated gut microbial perturbation/dysbiosis has been implicated in the pathobiology of sleep disturbance; however, evidence is scarce. Eighteen newly diagnosed rectal cancer patients (ages 52-81 years; 10 males) completed a sleep disturbance questionnaire and provided stool samples for 16s RNA gene sequencing during chemo-radiotherapy. Descriptive statistics, Wilcoxon test and regression analyses were computed. Regression analyses showed the Shannon's diversity index to be a significant factor associated with sleep disturbance. This preliminary work suggests that the biological "gut-brain axis" mechanism may be associated with symptoms of sleep disturbance.

Exploring the Relationship between Diarrhea and Fatigue that can occur during Cancer Treatment: Using Structural Equation Modeling.

OBJECTIVE: To examine the relationship of the symptoms of diarrhea and fatigue by testing a model that included multiple dimensions of the cancer related-symptom experience. METHODS: A secondary data analysis was conducted on data from the self-reports of 102 cancer patients co experiencing diarrhea and fatigue during treatment at a comprehensive cancer center in the Southeastern United States. Structural equational modeling was employed to examine the relationship between the 2variables. Fatigue and diarrhea were assessed using items from the Cancer Symptom Scale. RESULTS: The structural model results showed that (a) the model fit was adequate (b) diarrhea explained 7% of the variance in fatigue, and (c) the structural or path coefficient between diarrhea and fatigue was significant (0.267; p<0.05). Diarrhea had the strongest effect on fatigue interference (0.251). CONCLUSION: Diarrhea is a potential contributing factor to the symptom of fatigue and a potential target for interventions to prevent and ameliorate fatigue.