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

Shuai Ji; Shuangshuang Han; Lin Yu; Lijing Du; Yanting You; Jieyu Chen; Ming Wang; Shengwei Wu; Shasha Li; Xiaomin Sun; Ren Luo; Xiaoshan Zhao

doi:10.1016/j.phymed.2022.153940

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

Phytomedicine. 2022 Apr:98:153940. doi: 10.1016/j.phymed.2022.153940. Epub 2022 Jan 15.

Authors

Shuai Ji¹, Shuangshuang Han¹, Lin Yu², Lijing Du³, Yanting You¹, Jieyu Chen¹, Ming Wang⁴, Shengwei Wu², Shasha Li⁵, Xiaomin Sun¹, Ren Luo¹, Xiaoshan Zhao⁶

Affiliations

¹ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
² Department of Traditional Chinese Medicine, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou 510170, Guangdong, China.
³ School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200030, China.
⁴ Department of Traditional Chinese Medicine, Zhujiang Hospital of Southern Medical University, Guangzhou 510280, China.
⁵ The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
⁶ School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. Electronic address: zhaoxs0609@163.com.

PMID: 35104765
DOI: 10.1016/j.phymed.2022.153940

Abstract

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 predicted based on JWXYS treatment focused on purine metabolism, which was also enriched from cerebral metabolites regulated by JWXYS.

Conclusion: Our study suggests that L. animalis is involved in depression-like behaviors in mice. JWXYS 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.

Keywords: Depression-like behaviors; Full-length 16S rRNA sequencing; Jia Wei Xiao Yao San; Metabolome; Purine metabolism.