Bacopaside I alleviates depressive-like behaviors by modulating the gut microbiome and host metabolism in CUMS-induced mice

• Published in: Biomedicine & pharmacotherapy Vol. 170; p. 115679
• Main Authors: Wang, Jie, Xin, Jiayun, Xu, Xike, Chen, Wei, Lv, Yanhui, Wei, Yanping, Wei, Xintong, Li, Zhanhong, Ding, Qianqian, Zhao, Houyu, Wen, Yukun, Zhang, Xiuyun, Fang, Yiqun, Zu, Xianpeng
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.01.2024; Elsevier
• Subjects: Acetates - pharmacology; Animals; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Bacopaside I; Depression; Depression - metabolism; Fecal microbiota transplantation; Gastrointestinal Microbiome; Hypothalamo-Hypophyseal System; Lipidomics; Mice; Microbiota-gut-brain axis; Pituitary-Adrenal System; Short-chain fatty acids; Stress, Psychological - metabolism; Short-chain fatty acids; DSR; Microbiota-gut-brain axis; DG; PAS; Fecal microbiota transplantation; CUMS; Bacopaside I; ACTH; Depression; Lipidomics; IL-1β; IL-6; LPS; COVID-19; CORT; NF-κB; ZO-1; AB-PAS; TNF-α; ELSA; CRH; HPA; SCFAs
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115679

Bacopaside I (BSI) is a natural compound that is difficult to absorb orally but has been shown to have antidepressant effects. The microbiota-gut-brain axis is involved in the development of depression through the peripheral nervous system, endocrine system, and immune system and may be a key factor in the effect of BSI. Therefore, this study aimed to investigate the potential mechanism of BSI in the treatment of depression via the microbiota-gut-brain axis and to validate it in a fecal microbiota transplantation model. The antidepressant effect of BSI was established in CUMS-induced mice using behavioral tests and measurement of changes in hypothalamicpituitaryadrenal (HPA) axis-related hormones. The improvement of stress-induced gut-brain axis damage by BSI was observed by histopathological sections and enzyme-linked immunosorbent assay (ELISA). 16 S rDNA sequencing analysis indicated that BSI could modulate the abundance of gut microbiota and increase the abundance of probiotic bacteria. We also observed an increase in short-chain fatty acids, particularly acetic acid. In addition, BSI could modulate the disruption of lipid metabolism induced by CUMS. Fecal microbiota transplantation further confirmed that disruption of the microbiota-gut-brain axis is closely associated with the development of depression, and that the microbiota regulated by BSI exerts a partial antidepressant effect. In conclusion, BSI exerts antidepressant effects by remodeling gut microbiota, specifically through the Lactobacillus and Streptococcus-acetic acid-neurotrophin signaling pathways. Furthermore, BSI can repair damage to the gut-brain axis, regulate HPA axis dysfunction, and maintain immune homeostasis. [Display omitted]