Screening of Fecal Bacteroides Strains and Discovery of Bacteroides eggerthii S13-F8 with Protective Effects Against Chemotherapy-Induced Diarrhea.

Abstract

Chemotherapy-induced diarrhea (CID) is a frequent gastrointestinal side effect in cancer patients, particularly associated with the use of 5-fluorouracil (5-FU). This study aimed to isolate multiple Bacteroides strains from the feces of healthy individuals and identify Bacteroides eggerthii (B. eggerthii) S13-F8 as the optimal candidate for alleviating CID. Whole-genome sequencing of B. eggerthii S13-F8 was conducted to uncover its functional characteristics and explore the potential mechanisms underlying its protective effects against CID. The anti-CID efficacy of B. eggerthii S13-F8 was assessed using multiple parameters, including diarrhea severity, food intake, and body weight changes. Comprehensive analyses, including blood tests, intestinal histopathology, colon transcriptomics, and fecal metagenomics, were performed to elucidate its underlying mechanisms. In a 5-FU-induced mouse model, B. eggerthii S13-F8 significantly alleviated weight loss and diarrhea. Histological examination revealed that B. eggerthii S13-F8 preserved the villus height-to-crypt depth (V/C) ratio and protected goblet cells in colonic tissues. Gene expression analysis showed that B. eggerthii S13-F8 upregulated protective markers, such as Aqp8, Slc26a3, and mucin-related genes (TFF3, FCGBP, and Muc2), while downregulating pro-inflammatory mediators, including IL-1α, IL-22, and Cxcl2. Furthermore, B. eggerthii S13-F8 modulated gut microbiota composition by suppressing pathogenic bacteria (Pseudomonas aeruginosa, Salmonella, γ-Proteobacteria, and Shigella) and enriching beneficial taxa, such as Lactobacillus and Akkermansia muciniphila. In conclusion, B. eggerthii S13-F8 demonstrates significant potential in mitigating severe diarrhea caused by 5-FU chemotherapy, providing a strong foundation for its development as a live biotherapeutic for CID treatment.