Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression

Jingyi Xu; Lei Zhou; Zhaowei Chen; Yuezhu Wang; Fang Xu; Qun Kuang; Yixuan Zhang; Huajun Zheng

doi:10.3389/fphar.2024.1393874

Bacillus coagulans and Clostridium butyricum synergistically alleviate depression in a chronic unpredictable mild stress mouse model through altering gut microbiota and prefrontal cortex gene expression

Front Pharmacol. 2024 May 23:15:1393874. doi: 10.3389/fphar.2024.1393874. eCollection 2024.

Authors

Jingyi Xu¹, Lei Zhou², Zhaowei Chen², Yuezhu Wang², Fang Xu³, Qun Kuang⁴, Yixuan Zhang¹, Huajun Zheng^{2

3}

Affiliations

¹ School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Shenyang, China.
² Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Shanghai, China.
³ The Academician Workstation, Shanghai Fourth People's Hospital Affiliated to Tongji University, Shanghai, China.
⁴ Jiangsu Limited Company of Suwei Microbiology, Wuxi, China.

Abstract

Introduction: The prevalence of major depressive disorder (MDD) has gradually increased and has attracted widespread attention. The aim of this study was to investigate the effect of a probiotic compound consisting of Bacillus coagulans and Clostridium butyricum, on a mouse depression model. Methods: Mice were subjected to chronic unpredictable mild stress (CUMS) and then treated with the probiotics at different concentrations. And mice received behavior test such as forced swimming test and tail suspension test. After that, all mice were sacrificed and the samples were collected for analysis. Moreover, prefrontal cortex (PFC) gene expression and the gut microbiota among different groups were also analyzed. Results: Probiotics improved depressive-like behavior in CUMS mice, as indicated by decreased immobility time (p < 0.05) in the forced swimming test and tail suspension test. probiotics intervention also increased the level of 5-hydroxytryptamine (5-HT) in the prefrontal cortex and decreased the adrenocorticotropic hormone (ACTH) level in serum. In addition, by comparing the PFC gene expression among different groups, we found that the genes upregulated by probiotics were enriched in the PI3K-Akt signaling pathway in the prefrontal cortex. Moreover, we found that downregulated genes in prefrontal cortex of CUMS group such as Sfrp5 and Angpt2, which were correlated with depression, were reversed by the probiotics. Furthermore, the probiotics altered the structure of the gut microbiota, and reversed the reduction of cob(II)yrinate a,c-diamide biosynthesis I pathway in CUMS group. Several species like Bacteroides caecimuris and Parabacteroides distasoni, whose abundance was significantly decreased in the CUMS group but reversed after the probiotics intervention, showed significantly positive correlation with depression associated genes such as Tbxas1 and Cldn2. Discussion: These findings suggested that CUMS-induced depression-like behavior can be alleviated by the probiotics, possibly through alterations in the PFC gene expression and gut microbiota.

Keywords: Bacillus coagulans; CUMS; Clostridium butyricum; chronic unpredictable mild stress; depression; gut microbiota; probiotics; transcriptome.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Science and Technology Fundamental Resources Investigation Program of China (2019FY100700).