2. Academic Validation
  3. B.uniformis IM01-derived IAA alleviates asthma via AhR/NLRP3 pathways in mice

B.uniformis IM01-derived IAA alleviates asthma via AhR/NLRP3 pathways in mice

  • Cell Mol Life Sci. 2025 Nov 6;82(1):388. doi: 10.1007/s00018-025-05910-7.
Yujia He 1,  Tao Yang 1,  Jielan Mi 1 2,  Siqin He 1,  Zhihan Yang 1,  Simin Lu 1 3,  Kun Yue 1 3,  Yuanming Huang 1,  Liqiong Song 1,  Yuchun Xiao 1,  Zhihong Ren 4
Affiliations

Affiliations

  • 1 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China.
  • 2 Institute of Public Health, School of Medicine, Nankai University, Tianjin, 300071, PR China.
  • 3 Research Unite for Unknown Microbe, Institute of Pathogen Biology, Chinese Academy of Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, China.
  • 4 National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China. [email protected].
PMID: 41196415 DOI: 10.1007/s00018-025-05910-7
Abstract

Symbiotic flora exhibits a strong association with the pathogenesis of allergic disorders. Certain Bacteroides species have demonstrated potential in ameliorating allergic conditions. However, the specific role of Bacteroides uniformis in allergic asthma and its underlying mechanisms remain incompletely understood. This study demonstrates that oral administration of B.uniformis IM01 significantly enhanced the production of indole-3-acetic acid (IAA), suppressed airway inflammatory cell airway infiltration and aberrant T helper 2 (Th2) immune responses, and improved the epithelial barrier function in a murine model of asthma. Mechanistically, B.uniformis IM01 upregulated tryptophan metabolism, elevating IAA levels in both colon and serum, which activated the Aryl Hydrocarbon Receptor (AhR) and induced interleukin-22 (IL-22) production. Activated AhR may inhibit NF-κB/NLRP3 signaling pathway and facilitate the splenic differentiation of Foxp3+ regulatory T cells (Tregs), thus attenuating lung barrier dysfunction and improving allergic asthma symptoms. In summary, our results revealed that B.uniformis IM01 upregulated production of IAA to activate AhR leading to inhibited NF-κB/NLRP3-mediated immune responses, and ameliorated allergic asthma through the gut-lung axis.

Keywords

Barrier damage; Gut microbiome; Indole derivatives; Inflammasome; Metabolomics; Ovalbumin.

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