Clostridium butyricum miyairi 588 has preventive effects on chronic social defeat stress-induced depressive-like behaviour and modulates microglial activation in mice.

Recent studies have suggested the neuroprotective effects of Clostridium butyricum on mood disorders. However, the potential role of Clostridium butyricum in modulating the gut-brain-axis remains unknown. Here, we applied the commercial Clostridium butyricum Miyairi 588 (CBM588) strain to assess psychological behavioural alterations in mice exposed to chronic social defeat stress (CSDS). We found that preventive treatment with CBM588 for 28 days ameliorated depressive-like behaviours in CSDS mice. We showed that CSDS led to increases in cytokines (IL-1β, IL-6, and TNF-α), intestinal dysfunction and hippocampal microglial activation, while CBM588 partially relieved these alterations. By applying 16S sequencing, we found that Firmicutes was more abundant in the faeces of CBM588/CSDS mice than in the faeces of placebo/CSDS mice, and depression-like behaviours in the mice were correlated with certain strains (including Clostridium leptum, Blautia coccoides, Family_XIII_UCG-001, Candidatus Arthromitus sp-SFB-mouse-Japan and Streptococcus hyointestinalis) at the species level. Our results illustrated the preventive effect of CBM588 against stress, suggesting the beneficial role of CBM588 in regulating neuroinflammation via the gut-brain-axis. This study provides novel strategies for clinical and scientific investigations of depressive disorders.