Exploring the mechanism of antibiotic-exacerbated allergic rhinitis in mice based on untargeted metabolomics

AimTo investigate the mechanism underlying the exacerbation of allergic rhinitis (AR) in mice following antibiotic-induced gut microbiota depletion.MethodsOvalbumin (OVA)-induced AR mouse models and antibiotic cocktail-induced gut microbiota-depleted AR models were established. The frequency of nose-scratching and sneezing was recorded. Plasma OVA-specific immunoglobulin E (OVA-sIgE) levels and interleukin (IL)-6, IL-13, and IL-17 levels in bronchoalveolar lavage fluid (BALF) were measured using enzyme-linked immunosorbent assay (ELISA). Nasal mucosal pathology was evaluated via hematoxylin-eosin (HE) staining. Differential plasma metabolites were identified using untargeted metabolomics, and the associated pathways were predicted.ResultsAfter gut microbiota depletion, intestinal microbial diversity significantly decreased. Mice exhibited increased nose-scratching and sneezing frequencies, elevated plasma OVA-sIgE, and upregulated IL-6, IL-13, and IL-17 levels in BALF. Nasal mucosa displayed inflammatory lesions and goblet cell hyper-plasia. A total of 1 175 compounds were matched through a database of compounds, with 11 significantly altered metabolites: phenylpropanoids, polyketides, organic acids/derivatives, and lipids/lipid-like molecules were upregulated, while benzene-type compounds and organic oxygen compounds were downregulated. KEGG enrichment analysis revealed upregulated pathways including bile secretion, taste transduction, and glycerophospholipid metabolism.ConclusionsGut microbiota depletion exacerbates AR symptoms in mice, potentially by modulating metabolites (phenylpropanoids, polyketides, organic acids, lipids, benzene-type compounds) and pathways related to bile secretion, taste transduction, and glycerophospholipid metabolism.