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

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

  • Imeta. 2025 Feb 23;4(2):e70005. doi: 10.1002/imt2.70005.
Shiqi Liu 1 2 3,  Peiran Cai 1 2 3,  Wenjing You 1 2 3,  Mingshun Yang 1 2 3,  Yuang Tu 1 2 3,  Yanbing Zhou 1 2 3,  Teresa G Valencak 4,  Yingping Xiao 5,  Yizhen Wang 1 2 3,  Tizhong Shan 1 2 3
Affiliations

Affiliations

  • 1 College of Animal Sciences Zhejiang University Hangzhou China.
  • 2 Key Laboratory of Molecular Animal Nutrition (Zhejiang University) Ministry of Education Hangzhou China.
  • 3 Zhejiang Key Laboratory of Nutrition and Breeding for High-quality Animal Products Hangzhou China.
  • 4 Austrian Agency for Health and Food Safety Vienna Austria.
  • 5 State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products, Institute of Agro-product Safety and Nutrition Zhejiang Academy of Agricultural Sciences Hangzhou China.
PMID: 40236773 DOI: 10.1002/imt2.70005
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.

Keywords

2‐hydroxy‐4‐methylpentanoic acid; GADD45A; Wnt/β‐catenin signaling; intestinal barrier; metabolites; probiotics.

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