IM01 Alleviates Allergic Airway Inflammation Through Microbial and Metabolic Crosstalk Along the Gut-Lung Axis.

Abstract

Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut-lung axis. Whileis a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood.In this study, we investigated the protective effects and underlying mechanisms ofIM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach.Our results demonstrated that oral administration ofIM01 significantly attenuated airway inflammation, suppressed Th2-type immune responses, and reduced serum IgE levels. Crucially, our multi-omics integration revealed a coherent gut-lung axis narrative driven by microbial and metabolic crosstalk. Specifically, 16S rRNA sequencing indicated thatIM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such asand. This microbial restructuring was closely associated with a modulated cecal metabolic profile, as untargeted metabolomics exhibited a clear trend toward the restoration of key systemically active immunoregulatory metabolites, including indolelactic acid (ILA) and choline, which have been previously linked to the alleviation of AAI symptoms. Further linking this metabolic shift to respiratory immune tolerance, lung transcriptomic analysis showed that the treatment is strongly associated with the promotion of the differentiation of CD4T cells into Foxp3regulatory T cells (Tregs).Collectively, these findings suggest a novel potential pathway by whichIM01 modulates the gut-lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI.