β-Glucuronidase-Expressing Lactobacillus reuteri Triggers Irinotecan Enterotoxicity Through Depleting the Regenerative Epithelial Stem/Progenitor Pool.

ABSTRACT: Irinotecan (CPT11)-induced diarrhea affects 80-90% of cancer patients due to β-glucuronidase (GUS) converting 7-ethyl-10-hydroxycamptothecin glucuronide (SN38G) to 7-ethyl-10-hydroxycamptothecin (SN38). It remains unclear whether SN38 impacts the homeostasis between gut microbiota and mucosal stem cell niche. This study explores the crosstalk between gut microbiota and intestinal stem cells (ISCs) in intestinal mucositis triggered by CPT11 chemotherapy. CPT11-treated mice exhibited significant colon shortening, inflammatory infiltration, intestinal barrier dysfunction, and ISC impairment, which correlated with gut dysbiosis, enrichment of GUS-expressing bacteria, and intraluminal SN38 accumulation. In contrast, antidiarrheal (Xianglian pill) treatment alleviated SN38-induced enterotoxicity

SUBMITTER: Yue B 

PROVIDER: S-EPMC12245021 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature