You-Gui-Wan ameliorates house dust mite-induced allergic asthma via modulating amino acid metabolic disorder and gut dysbiosis

IntroductionAllergic asthma is a worldwide health problem, and its etiology remains incompletely understood. Besides, as current therapies for allergic asthma mainly rely on administration of glucocorticoids and have many side effects, new therapy is needed. You-Gui-Wan (YGW), a traditional Chinese herbal remedy, has been used for boosting Yang, enhancing immunity and treating allergic asthma.ObjectivesThis study aims to explore the molecular changes during the development of allergic asthma and investigate the potential bio-signatures and the effect of YGW on house dust mite (HDM)-induced chronic allergic asthma in mice.MethodsDermatophagoides pteronyssinus (Der p), one of HDMs, was intratracheally administered once a week for a total of 7 treatments over 6 consecutive weeks to induce allergic asthma in mice. Serum metabolomics was analyzed by LC-QTOF-MS/MS. 16S rRNA-based microbiome profiling was used to analyze gut microbiota, and the correlation between metabolomic signatures and microbial community profiling was explored by Spearman correlation analysis.ResultsSerum metabolomic analysis revealed that 10 identified metabolites — acetylcarnitine, carnitine, hypoxanthine, tryptophan, phenylalanine, norleucine, isoleucine, betaine, methionine, and valine, were markedly elevated by Der p. These metabolites are mainly related to branch-chain amino acid (BCAA) metabolism, aromatic amino acid (AAA) biosynthesis, and phenylalanine metabolism. YGW administration reversed 7 of the 10 identified metabolites and chiefly affected BCAA metabolism. 16S DNA sequencing revealed that YGW profoundly changed Der p-induced gut microbiota composition. Multiple correlation analysis indicated 10 selected metabolites have a good correlation with gut microbiota.ConclusionDer p induced BCAA metabolic deviation in allergic asthma mice, and YGW administration effectively ameliorated the AA metabolic disorder, and improved gut dysbiosis. This study paves the way towards the interactions of Der-p on microbiome and gut microbiota, and the effects of YGW treatment as well as provides a support for YGW administration with potential benefits for allergic asthma.