Enhancement of gut barrier integrity by a Bacillus subtilis secreted metabolite through the GADD45A‐Wnt/β‐catenin pathway

• DOI: 10.1002/imt2.70005
• Publication Date: 2025-02-23T11:20:02Z
• Authors: Shiqi Liu; Peiran Cai; Wenjing You; Mingshun Yang; Yuang Tu; Yanbing Zhou; Teresa G. Valencak; Yingping Xiao; Yizhen Wang; Tizhong Shan
• Keywords: Metabolite profiling

Inflammatory bowel disease (IBD) represents a significant challenge to global health, characterized by intestinal inflammation, impaired barrier function, and dysbiosis, with limited therapeutic options. In this study, we isolated novel strain of Bacillus subtilis (B. subtilis) observed promising effects in protecting against disruption the gut barrier. Our findings indicate that enhancement function is primarily attributed its metabolites. We identified metabolite, 2-hydroxy-4-methylpentanoic acid (HMP), derived from B. subtilis, significantly improved function. also show growth arrest DNA damage 45A (GADD45A) key regulator mucosal integrity, which activated HMP subsequently activates downstream Wnt/β-catenin pathway. potentially contribute development probiotics-derived metabolites or targeted "postbiotics" as therapeutics for treatment prevention IBD other diseases associated dysfunction.