Microbiota-mediated metabolic alterations reveal bidirectional regulation of the gut-nose axis in mice with allergic rhinitis

Microbes and their metabolites are implicated in respiratory diseases, including allergic rhinitis (AR); however, the interaction between the gut and respiratory tract and the role of microbes remains unclear. We investigated the gut and nasal microbiota variations between AR and control mice and their role in the bidirectional regulation of the gut-nasal axis. We validated the OVA-induced establishment of an AR mouse model based on nasal symptoms and histopathology. The microbiota and metabolites in the feces and nasal lavage fluid were analyzed, and a correlation analysis was performed. Structural changes in the colonic and nasal mucosa were examined using electron microscopy, and ZO-1 and Claudin 1 protein expression was assessed using immunofluorescence and western blotting. RNA-seq identified changes in gene expression in the nasal mucosa. Mendelian randomization analysis was applied to exploit the causal relationship between gut microbiota, gut microbiota-derived metabolites and AR. AR mice exhibited aggravated nasal symptoms, local histological disruption, and inflammatory cell infiltration in the nasal mucosa and gut tissues, with significant changes in the microbiota and metabolites at both sites. Correlation analysis revealed that gut microbes influenced fecal and nasal lavage fluid metabolite changes and vice versa. AR mice also have impaired nasal mucosal and colonic interepithelial junctions, reduced ZO-1 and Claudin 1 expression, and upregulated immune-inflammatory pathways in the nasal mucosa. The microbiota in the gut and nasal cavity interact bidirectionally, coordinating the gut-nasal axis and contributing to AR pathology. These findings provide insights for advancing AR research and management.