Comprehensive gut microbiota and metabolomics for evaluating the mechanism of Qing'e Pill in ameliorating depression-like behaviors of CUMS mice.

Abstract

As a kidney-yang tonifying Chinese medicine prescription, Qing'e Pill (QP) has been shown to exhibit antidepressant effects. However, its therapeutic mechanisms remain unclear. This study employed antibiotic-treatment to evaluate the importance of gut microbiota in QP's effect, and combined metabolomics and 16S rDNA sequencing to investigate the potential mechanism of QP in a chronic unpredictable mild stress (CUMS)-induced depression mouse model. QP administration significantly ameliorated depressive-like behaviors and neuroinflammation in CUMS mice, but not in antibiotic-treated CUMS mice. Gut microbiota analysis revealed that QP increased the abundance of short-chain fatty acids (SCFAs)-producing bacteria (Lachnospiraceae NK4A136 group), and elevated fecal butyrate level. Untargeted metabolomics analysis identified 16 differential metabolites including carnitine, acetylcarnitine and palmitoylcarnitine, primarily associated with fatty acid oxidation. Notably, Spearman's correlation analysis demonstrated significant positive associations between Lachnospiraceae NK4A136 group, butyrate, and palmitoylcarnitine levels. Our findings wish to discover the potential mechanism of QP treatment on depression and further expand its clinical application.