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

Journal: Biomedicine & Pharmacotherapy Publication Year: 2024 | Volume: 170 | Issue: No issue number listed | Article Number: 115679 Authors: Jie Wang, Jiayun Xin, Xike Xu, Wei Chen, Yanhui Lv, Yanping Wei, Xintong Wei,...

Jul 28, 2026 | 1 min read

Research Gist

This preclinical study examined whether bacopaside I, an isolated compound associated with Bacopa monnieri, could improve depression-like behaviour in mice exposed to chronic unpredictable mild stress. Oral bacopaside I treatment improved behavioural outcomes and was associated with changes in gut bacteria, increased short-chain fatty acids, particularly acetic acid, improved intestinal-barrier integrity, reduced inflammatory disruption, more stable HPA-axis activity and partial correction of altered lipid metabolism.

Fecal microbiota transplantation showed that the bacopaside I-modified microbiome transferred part of the behavioural benefit, supporting involvement of the microbiota–gut–brain axis.

Key Learnings

  • The study tested isolated bacopaside I, not a whole Brahmi or Bacopa monnieri extract.
  • Mice with CUMS-induced depression-like behaviour received bacopaside I orally at 45 mg/kg for two weeks.
  • Treatment improved behavioural measures and helped regulate stress-related HPA-axis hormones.
  • Bacopaside I altered gut-microbial composition and increased bacteria identified by the authors as potentially beneficial.
  • Short-chain fatty acids increased, particularly acetic acid, alongside changes involving Lactobacillus and Streptococcus.
  • The treatment reduced stress-associated intestinal-barrier damage, plasma lipopolysaccharide and inflammatory disruption, while also modifying altered lipid metabolism.
  • Fecal microbiota transplantation reproduced only part of the behavioural effect. This supports microbiome involvement but does not establish human antidepressant efficacy or safety, and no dedicated clinical tolerability assessment was performed.
Research Summary