Jia Wei Xiao Yao San ameliorates chronic stress-induced depression-like behaviors in mice by regulating the gut microbiome and brain metabolome in relation to purine metabolism

作者：Shuai Ji, Shuangshuang Han, Lin Yu, Lijing Du, Yanting You, Jieyu Chen, Ming Wang, Shengwei Wu, Shasha Li, Xiaomin Sun, Ren Luo, Xiaoshan Zhao · 发表于：Phytomedicine · 年份：2022 · DOI：10.1016/j.phymed.2022.153940 · 被引用次数：37 · 研究领域：Gut microbiota and health、Tryptophan and brain disorders、Metabolomics and Mass Spectrometry Studies

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 (JWXYS) is considered a potential antidepressant. However, the pharmacological mechanisms of JWXYS have not yet been clarified. PURPOSE: This study aimed to explore the effects of JWXYS 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 JWXYS 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...