Latilactobacillus curvatus IM01 Alleviates Allergic Airway Inflammation Through Microbial and Metabolic Crosstalk Along the Gut–Lung Axis

<b>Background:</b> Gut microbiota dysbiosis is critically implicated in the pathogenesis of allergic airway inflammation (AAI) via the gut-lung axis. While <i>Latilactobacillus curvatus</i> is a promising probiotic candidate, its specific immunomodulatory mechanisms in respiratory diseases remain poorly understood. <b>Objective:</b> In this study, we investigated the protective effects and underlying mechanisms of <i>L. curvatus</i> IM01 in an ovalbumin (OVA)-induced murine AAI model using an integrated multi-omics approach. <b>Results:</b> Our results demonstrated that oral administration of <i>L. curvatus</i> IM01 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 that <i>L. curvatus</i> IM01 was closely linked to structural shifts in the gut microbial community, notably characterized by an enrichment trend for beneficial genera such as <i>Odoribacter</i> and <i>Lactobacillus</i>. 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 CD4⁺ T cells into Foxp3⁺ regulatory T cells (Tregs). <b>Conclusions:</b> Collectively, these findings suggest a novel potential pathway by which <i>L. curvatus</i> IM01 modulates the gut-lung axis through coordinated microbial and metabolic interventions, highlighting its potential as a therapeutic functional food ingredient for AAI.