Mitigation of chemotherapy-induced gut dysbiosis and diarrhea by supplementation with heat-killed Bacteroides fragilis

作者：Xinwen Yan, Xinlong Lin, Jianhua Wu, Lijun Zheng, Yangyang Liu, Fang Wu, Ying Lin, Yishi Lu, Chongyang Huang, Binhai Shen, Hongbin Liu, Ruo Huang, Fengyi Hou, Qian Zhou, Mengyao Song, Ke Liu, Fangqing Zhu, Sheng Li, Yuqing Lin, W. Wang, Ping Li, Wangjun Liao, Fachao Zhi · 发表于：BMC Medicine · 年份：2025 · DOI：10.1186/s12916-025-04233-5 · 被引用次数：11 · 研究领域：Gut microbiota and health、Clostridium difficile and Clostridium perfringens research、Probiotics and Fermented Foods

BACKGROUND: The role of gut microbial dysbiosis in chemotherapy-induced diarrhea (CID) pathogenesis remains unclear in humans. This study investigates gut microbiota alterations in CID patients and evaluates the therapeutic potential of probiotic supplementation. METHODS: To establish a paired cohort for longitudinal comparison and minimize confounding factors in assessing CID-related microbiota changes, strict inclusion/exclusion criteria were applied to gastrointestinal cancer patients. Fecal samples from eligible participants underwent shotgun metagenomic sequencing to comprehensively profile the gut microbiome composition and function. To evaluate probiotic efficacy and mechanisms, we utilized 6-8-week-old male BALB/c and C57BL/6 mice in established 5-FU- or CPT-11-induced CID models. Probiotic efficacy was assessed using primary (diarrhea severity) and secondary endpoints (body weight change, intestinal permeability). Mechanistic studies were conducted in murine models, complemented by IEC-6 cells and intestinal organoid experiments to elucidate microbiota-host interactions. RESULTS: Analysis of paired fecal samples (pre- and post-chemotherapy) from 30 gastrointestinal cancer patients (n = 60) revealed chemotherapy-induced reduction of Bacteroides fragilis (B. f) via metagenomics sequencing, with baseline B. f relative abundance negatively correlating with CID severity (r = - 0.93, p = 3.1e - 12). Building on these clinical observations, in 5-FU/CPT-11-induced CID murine...