Effects of azithromycin on alleviating airway inflammation in asthmatic mice by regulating airway microbiota and metabolites

Background:Asthma is a chronic respiratory disease with increasing global prevalence, often linked to a disrupted airway microbiota. Azithromycin has shown promise in asthma treatment，but whether its effect is owing to its antimicrobial capacity remained largely unknown.Methods: A house dust mite (HDM)-induced asthmatic mouse model was used to evaluate the effects of azithromycin on airway inflammation and microbiota. Mice were divided into control, HDM-induced asthma, HDM + azithromycin, and azithromycin alone groups. Airway microbiota was analyzed using 16S rRNA sequencing, and metabolomic profiles were assessed via LC-MS/MS.Results:Azithromycin alleviated type 2 airway inflammation in HDM-induced asthma, restoring microbiota diversityby modulating specific genera, including Streptococcus, Staphylococcus, Ruminococcus, Coprococcus, Bifidobacterium etc. Combination analysis with metabolomicsrevealed that azithromycin significantly regulated airway microbiota associated sphingomyelin metabolism.Conclusion: Azithromycin's therapeutic effects in asthma are associated withits ability to regulate airway microbiota and its associatedsphingomyelin metabolism, highlighting the potential for microbiota-targeted therapies in asthma.