Biliverdin targeting TcdB-DRBD inhibits Clostridioides difficile virulence and restores gut microbiota in Mongolian gerbils (Meriones unguiculatus).

ABSTRACT: The incidence of Clostridioides difficile infection (CDI) has been rising globally in recent years. Treating CDI is complicated by antibiotic-induced disruption of the normal gut microbiota, which promotes CDI recurrence and increases the risk of therapeutic failure. We used an AI-assisted approach to screen small molecule inhibitors targeting the receptor binding domain of toxin B (TcdB). Biliverdin (BV) had strong binding affinities with all TcdB variants. In vitro results showed that BV exhibited no cytotoxic effects on cells and didn't affect growth of C. difficile, yet markedly suppressed cytotoxic effects induced by TcdB1-4. Encapsulating BV in intestinal epithelial cell-derived extracellular vesicles (I-EVs) significantly recovered body weight, enhanced survival rate, reduced TcdB l

SUBMITTER: Wan S 

PROVIDER: S-EPMC12647718 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature