Abstract:Objective: To investigate the intervention effect of sulforaphane (SFN) on polycyclic aromatic hydrocarbons (PAHs)-related asthma by regulating gut microbiota abundance and influencing metabolic functions, as well as its underlying mechanisms. Methods:SMouse models of prenatal PAHs exposure and asthma were established, with SFN intervention. Lung pathological analysis, 16S rRNA sequencing, and ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS)-based metabolomics were conducted to evaluate the effects of SFN on gut microbiota structure and metabolic pathways. Results:SSFN alleviated pulmonary inflammatory infiltration in PAHs-exposed asthmatic mice. Analyses of α-diversity, β-diversity, species abundance, and functional prediction indicated that SFN intervention had certain effects on the structure, composition, and functions of gut microbiota. Metabolomics analysis showed that SFN intervention downregulated abnormally elevated metabolites (such as hypoxanthine and cyclic adenosine monophosphate) in metabolic pathways including purine metabolism and bile acid metabolism. Correlation analysis further revealed that SFN could partially reverse the changes in gut microbiota and metabolism induced by PAHs exposure. Conclusion:SSFN improved PAHs-exposed offspring asthma by remodeling gut microbiota structure and regulating key metabolic pathways (such as purine metabolism), providing an innovative theoretical basis for the preventive intervention and precision treatment of childhood asthma.