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

Abstract 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/β‐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.

• Publication year

  2025

• Venue

  iMeta

• Publication date

  2025-02-23

• Fields of study

  Biology, Medicine, Environmental Science

• Identifiers
  DOI 10.1002/imt2.70005PMID 40236773PMCID 11995189
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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