Gut Microbiota and Depressive Symptoms at the End of CRT for Rectal Cancer: A Cross-Sectional Pilot Study.

BACKGROUND: The role of alterations in gut microbiota composition (termed dysbiosis) has been implicated in the pathobiology of depressive symptoms; however, evidence remains limited. This cross-sectional pilot study is aimed at exploring whether depressive symptom scores changed during neoadjuvant chemotherapy and radiation therapy to treat rectal cancer, and if gut microbial taxa abundances and predicted functional pathways correlate with depressive symptoms at the end of chemotherapy and radiation therapy. METHODS: 40 newly diagnosed rectal cancer patients (ages 28-81; 23 males) were assessed for depressive symptoms using the Hamilton Rating Scale for Depression (HAM-D) and provided stool samples for 16S rRNA sequencing. Gut microbiome data were analyzed using QIIME2, and correlations and regression analyses were performed in R. RESULTS: Participants had significantly higher depressive symptoms at the end as compared to before CRT. The relative abundances of Gemella, Bacillales Family XI, Actinomyces, Streptococcus, Lactococcus, Weissella, and Leuconostocaceae were positively correlated (Spearman's rho = 0.42 to 0.32), while Coprobacter, Intestinibacter, Intestimonas, Lachnospiraceae, Phascolarctobacterium, Ruminiclostridium, Ruminococcaceae (UCG-005 and uncultured), Tyzzerella, and Parasutterella (Spearman's rho = -0.43 to - 0.31) were negatively correlated with HAM-D scores. Of the 14 predicted MetaCyc pathways that correlated with depressive symptom scores at the end of CRT, 11 (79%) were associated with biosynthetic pathways. CONCLUSIONS: Significant bacterial taxa and predicted functional pathways correlated with depressive symptoms at the end of chemotherapy and radiation therapy for rectal cancer which warrants further examination and replication of our findings.

Changes in Gut Microbiome Associated With Co-Occurring Symptoms Development During Chemo-Radiation for Rectal Cancer: A Proof of Concept Study.

PURPOSE: To examine a) whether there are significant differences in the severity of symptoms of fatigue, sleep disturbance, or depression between patients with rectal cancer who develop co-occurring symptoms and those with no symptoms before and at the end of chemotherapy and radiation therapy (CRT); b) differences in gut microbial diversity between those with co-occurring symptoms and those with no symptoms; and c) whether before-treatment diversity measurements and taxa abundances can predict co-occurrence of symptoms. METHODS: Stool samples and symptom ratings were collected from 31 patients with rectal cancer prior to and at the end of (24-28 treatments) CRT. Descriptive statistics were computed and the Mann-Whitney U test was performed for symptoms. Gut microbiome data were analyzed using R's vegan package software. RESULTS: Participants with co-occurring symptoms reported greater severity of fatigue at the end of CRT than those with no symptoms. Bacteroides and Blautia2 abundances differed between participants with co-occurring symptoms and those with no symptoms. Our random forest classification (unsupervised learning algorithm) predicted participants who developed co-occurring symptoms with 74% accuracy, using specific phylum, family, and genera abundances as predictors. CONCLUSION: Our preliminary results point to an association between the gut microbiota and co-occurring symptoms in rectal cancer patients and serves as a first step in potential identification of a microbiota-based classifier.