Combining Fecal Metabolomics and Gut Microbiome to Investigate the Anti-Depression Mechanism of Kai–Xin–San

Vollständiger Abstract

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Abstract Objective: Kai–Xin–San (KXS) is a traditional Chinese medicine that has been used for thousands of years to treat depression. However, the underlying mechanisms and full range of effects of KXS on depression remain unclear. Materials and Methods: A growing body of evidence suggests that the gut microbiota may interact with the brain and contribute to the development of mental disorders, such as depression and anxiety. Therefore, in this study, we employed a combined microbiomics and metabolomics approach to investigate the antidepressant effects of KXS and explore its underlying mechanisms. Depression models were established using chronic unpredictable mild stress combined with single-cage rearing to observe the effects of KXS on the behavior, fecal metabolites, and microbiota of model animals. Results: KXS had a significant therapeutic effect on depressed rats, as demonstrated by improvements in depressive behavior, reduced neuroinflammation, and restoration of intestinal damage. Metabolomics and microbiomics analyses indicated that KXS significantly altered 24 endogenous metabolites and restored the intestinal microbiota balance in depressed rats. The targeted metabolomics results demonstrated that KXS intervention reversed changes in important microbial metabolites, such as bile acids, and metabolites related to the tryptophan pathway. Conclusions: Overall, these findings establish a foundation for the advancement of depression treatment. Additionally, it highlights the importance of the gut microbiota and their metabolites in disease management, providing novel insights and approaches for the etiology, prevention, and treatment of depression.