Background: The pathogenesis of depression remains largely unknown. Accumulating evidence demonstrates the existence of a complex relationship between gut microbiome composition and brain functions. Jia Wei Xiao Yao San is considered a potential antidepressant. However, the pharmacological mechanisms of Jia Wei Xiao Yao San have not yet been clarified.
Purpose: This study aimed to explore the effects of Jia Wei Xiao Yao San on chronic stress-induced depression-like behaviors in mice.
Methods: A chronic restraint stress mouse model of depression was established. JWXYS was administered, and the responses of these mice to treatment were evaluated through several behavioral tests. The activity of astrocytes and microglia was detected by specific fluorescent labels. Inflammatory cytokines were quantified in intestinal and cerebral tissues. An integrated approach with full-length 16S rRNA sequencing and different types of untargeted metabolomics was conducted to investigate the relationship between the gut microbiome at the species level, metabolic brain functions, and JWXYS.
Results: We found that behavioral symptoms were associated with the relative abundance of Lactobacillus animalis. After Jia Wei Xiao Yao San treatment, the relative abundance of Ileibacterium valens with enzymes potentially involved in purine metabolism was also described.
The activation of astrocytes and microglia was negatively correlated with the relative abundance of L. animalis. Combined with network pharmacological analysis, several targets predicted based on Jia Wei Xiao Yao San treatment focused on purine metabolism, which was also enriched from cerebral metabolites regulated by Jia Wei Xiao Yao San.
Conclusion: Our study suggests that L. animalis is involved in depression-like behaviors in mice. Jia Wei Xiao Yao San increases the abundance of I. valens with potential enzymes in relation to cerebral purine metabolism, which is positively correlated with the activation of astrocytes in the amygdala.