Early-life antibiotic exposure promotes house dust mite-induced allergic airway inflammation by impacting gut microbiota and lung lipid metabolism

Asthma is a chronic inflammatory respiratory disease. Early-life antibiotic exposure is a unique risk factor for the incidence and severity of asthma later in life. Perturbations in microbial–metabolite–immune interaction caused by antibiotics are closely associated with the pathogenesis of allergy and asthma. We investigated the effect of early intervention with common oral antibiotics on later asthma exacerbations and found that different antibiotic exposures can amplify different types of immune responses induced by HDM. Cefixime (CFX) promoted a biased type 2 inflammation, azithromycin (AZM) enhanced Th17 immune response, and cefuroxime axetil (CFA) induced eosinophils recruitment. Moreover, early-life antibiotic exposure can have short- and long-term effects on the abundance, composition, and diversity of the gut microbiota. In the model of CFX-promoted type 2 airway inflammation, fecal metabolomics indicated abnormal lipid metabolism and T cell response. Lipidomic also suggested allergic airway inflammation amplified by CFX is closely associated with abnormal lipid metabolism in lung tissues. Moreover, abnormalities in lipid metabolism–related genes (LMRGs) were found to have cellular heterogeneity be associated with asthma severity by bioinformatics analysis.