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

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.