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

文献类型： 外文期刊

第一作者： Liu, Shiqi

作者： Liu, Shiqi;Cai, Peiran;You, Wenjing;Yang, Mingshun;Tu, Yuang;Zhou, Yanbing;Wang, Yizhen;Shan, Tizhong;Liu, Shiqi;Cai, Peiran;You, Wenjing;Yang, Mingshun;Tu, Yuang;Zhou, Yanbing;Wang, Yizhen;Shan, Tizhong;Liu, Shiqi;Cai, Peiran;You, Wenjing;Yang, Mingshun;Tu, Yuang;Zhou, Yanbing;Wang, Yizhen;Shan, Tizhong;Valencak, Teresa G.;Xiao, Yingping

作者机构：

关键词： 2-hydroxy-4-methylpentanoic acid; GADD45A; intestinal barrier; metabolites; probiotics; Wnt/beta-catenin signaling

期刊名称：IMETA （ 影响因子：33.2； 五年影响因子：33.2 ）

ISSN： 2770-5986

年卷期： 2025 年 4 卷 2 期

页码：

收录情况： SCI

摘要： 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 a novel strain of Bacillus subtilis (B. subtilis) and observed promising effects in protecting against disruption of the gut barrier. Our findings indicate that the enhancement of intestinal barrier function is primarily attributed to its metabolites. We identified a novel metabolite, 2-hydroxy-4-methylpentanoic acid (HMP), derived from B. subtilis, that significantly improved intestinal barrier function. We also show that growth arrest and DNA damage 45A (GADD45A) is a key regulator of mucosal barrier integrity, which is activated by HMP and subsequently activates the downstream Wnt/beta-catenin pathway. Our findings potentially contribute to the development of probiotics-derived metabolites or targeted "postbiotics" as novel therapeutics for the treatment or prevention of IBD and other diseases associated with intestinal barrier dysfunction.

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