Muribaculum intestinale alleviates depressive-like behaviors by inhibiting Th17 cell differentiation and M1 microglia polarization.

Abstract

BACKGROUND: Gut microbiota dysbiosis has been implicated in the pathogenesis of depression. Our previous studies identified loganin as a potential antidepressant agent; however, its oral bioavailability is low. Whether loganin alleviates depression via modulation of the gut microbiota remains unclear. METHODS: Chronic unpredictable stress mice model was used to evaluate the antidepressant-like effects of loganin. To determine the role of gut microbiota, mice were treated with an antibiotic cocktail (ABX) to deplete microbiota. Fecal microbiota transplantation (FMT) from loganin-treated donors and Muribaculum intestinale (M. intestinale) were performed to assess microbial contributions. RESULTS: Loganin exerted antidepressant-like effects by modulating gut microbiota, as evidenced by reduced efficacy in ABX-treated mice and behavioral improvements in recipients of FMT from loganin-treated donors. Loganin modulated gut microbiota composition particularly increasing the abundance of Muribaculum, and increased short-chain fatty acids (SCFAs). M. intestinale alleviated depressive-like behaviors, prompted the butyrylation of RORγt, inhibited Th17 cells differentiation, and suppressed M1 microglia polarization. Importantly, overexpression of RORγt attenuated the behavioral benefits of M. intestinale. CONCLUSION: Loganin exerts antidepressant-like effects by enriching Muribaculum and SCFAs, thereby inhibiting Th17 cell differentiation and M1 microglia polarization. M. intestinale may represent a promising microbial-based therapeutic strategy for depression.