Integrative metabolomic and microbiomic profiling: Unveiling the therapeutic mechanisms of Yangyinqingfei Decoction in acute lung injury

Abstract

Acute lung injury (ALI) is a severe inflammatory condition characterized by disruption of the alveolar-capillary barrier, leading to impaired gas exchange and respiratory failure. The gut-lung axis has emerged as a crucial player in the pathogenesis of ALI, highlighting the potential therapeutic value of modulating gut microbiota and associated metabolic pathways. This study aimed to investigate the mechanisms underlying the protective effects of Yangyinqingfei Decoction (YYQFD) in treating ALI from the perspective of the gut-lung axis using an integrative multi-omics approach. Eight key gut microbiota genera were identified and associated with YYQFD treatment, including Lachnospiraceae, Prevotellaceae_NK3B31_group, Lachnospiraceae_NK4A136_group, and unclassified_Eubacterium_coprostanoligenes_group, etc. Metabolomic analysis revealed significant regulation of purine metabolism and pyrimidine metabolism pathways by YYQFD, involving metabolites such as xanthine, inosine, hypoxanthine, guanine, deoxyadenosine, thymine, and thymidine. Correlation analysis demonstrated significant associations between specific gut microbiota and metabolites, suggesting their potential as diagnostic or therapeutic targets. Furthermore, the mediation analysis revealed that YYQFD might regulate deoxyadenosine and L-isoleucine levels via the unclassified_Eubacterium_Coprostanoligenes_group and unclassified_Clostridia_vadinBB60_group, contributing to its therapeutic effects in ALI. This finding highlights the importance of the gut-lung axis in the therapeutic mechanisms of YYQFD and provides insights for future research and development of targeted interventions.