Gut microbiome and tissue metabolomics reveal the compatibility effects of Xiaoyaosan on depression based on "gut-liver-kidney" axis

Xiaojie Liu; Xiaoling Wu; Senyan Wang; Xuemei Qin

doi:10.1016/j.phymed.2022.154628

Gut microbiome and tissue metabolomics reveal the compatibility effects of Xiaoyaosan on depression based on "gut-liver-kidney" axis

Phytomedicine. 2023 Mar:111:154628. doi: 10.1016/j.phymed.2022.154628. Epub 2023 Jan 20.

Authors

Xiaojie Liu¹, Xiaoling Wu², Senyan Wang², Xuemei Qin²

Affiliations

¹ Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China; Institute of Biomedicine and Health, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China. Electronic address: liuxiaojie@sxu.edu.cn.
² Modern Research Center for Traditional Chinese Medicine, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China; The Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China; Institute of Biomedicine and Health, Shanxi University, No. 92, Wucheng Rd. Xiaodian Dist. Taiyuan 030006, Shanxi, China.

PMID: 36731299
DOI: 10.1016/j.phymed.2022.154628

Abstract

Background: Depression affects not only the central nervous system, but also the peripheral system. Xiaoyaosan (XYS), a classical traditional Chinese medicine (TCM) prescription, exhibits definite anti-depression effects demonstrated both clinically and experimentally. However, its compatibility has not been entirely revealed due partly to the complex compositions of herbs contained.

Aim: Based on the strategy of "Efficacy Group", this study aimed to reveal the compatibility of XYS from the perspective of "gut-liver-kidney" axis.

Methods: Firstly, XYS was divided into two efficacy groups, i.e. Shugan (SG) and Jianpi (JP) groups. Classic behaviors of rats were measured to confirm the anti-depression effects of XYS and its two efficacy groups. On top of this, gut microbiota analysis and kidney metabolomics were performed by 16S rRNA sequencing and ¹H NMR, respectively.

Results: We found that XYS and its efficacy groups significantly regulated the abnormalities of behaviors and kidney metabolism of depressed rats, as well as intestinal disorders, but to different degrees. The regulatory effects of XYS and its efficacy groups on behaviors and kidney metabolomics of depressed rats had the same order, i.e. XYS > SG > JP, while the order of regulating gut microbiota was XYS > JP > SG. Both XYS and its efficacy groups significantly ameliorated gut microbiota disturbed, especially significant modulation of Peptostreptococcaceae. XYS significantly regulated nine kidney metabolites, while SG and JP regulated four and five differential metabolites, respectively, indicating that the two efficacy groups synergistically exhibited anti-depression effects, consequently contributing to the overall anti-depression effects of XYS.

Conclusion: The current findings not only innovatively demonstrate the anti-depression effects and compatibility of XYS from the perspective of "gut-liver-kidney" axis, comprehensively using "Efficacy Group" strategy, macro behavioristics, metabolome and microbiome, and also provide a new perspective, strategy, and methodology for studying complex diseases and the compatibility of TCMs.

Keywords: Compatibility; Efficacy groups; Metabolomics; Microbiome; Xiaoyaosan; “gut-liver-kidney” axis.

MeSH terms

Animals
Antidepressive Agents / pharmacology
Drugs, Chinese Herbal* / pharmacology
Gastrointestinal Microbiome*
Liver
Metabolomics / methods
RNA, Ribosomal, 16S
Rats

Substances

xiaoyaosan
Antidepressive Agents
RNA, Ribosomal, 16S
Drugs, Chinese Herbal