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

Asthma is a chronic respiratory disease with increasing global prevalence, often linked to disrupted airway microbiota. Azithromycin has shown promise in asthma treatment, but whether its effect is owing to its antimicrobial capacity remains largely unknown. 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 liquid chromatography-tandem mass spectrometry. Azithromycin alleviated type 2 airway inflammation in HDM-induced asthma, restoring microbiota diversity by modulating specific genera, including Streptococcus, Staphylococcus, Ruminococcus, Coprococcus, Bifidobacterium, etc. Combination analysis with metabolomics revealed that azithromycin significantly regulated airway microbiota-associated sphingomyelin metabolism. Azithromycin's therapeutic effects in asthma are associated with its ability to regulate airway microbiota and its associated sphingomyelin metabolism, highlighting the potential for microbiota-targeted therapies in asthma.