Faecalibacterium prausnitzii and its metabolite butyrate ameliorate psychological stress-induced obesity.

OBJECTIVE

Although evidence indicates that modulating gut microbiota may mitigate psychological stress-induced obesity, the specific gut microbes and their mechanistic pathways remain unclear.

DESIGN

This study first examined the relationships between gut microbes, particularly Faecalibacterium prausnitzii (F.prausnitzii), psychological stress, and indicators of adiposity in adolescents, utilizing both cross-sectional (n = 124) and prospective cohort (n = 51) data. Second, fecal microbiota transplantation (FMT) was performed to investigate whether psychological stress induces obesity through alterations in gut microbiota. Third, using a chronic corticosterone administration mouse model to simulate psychological stress-induced obesity, we evaluated the therapeutic potential of F.prausnitzii and its primary metabolite butyrate in reversing corticosterone-induced obesity. The underlying mechanisms were further elucidated in vitro using mouse 3 T3-L1 adipocytes.

RESULTS

Cross-sectional data indicated inverse associations between the abundance of Faecalibacterium and both psychological stress and indicators of adiposity. Additionally, prospective cohort data demonstrated that baseline psychological stress inversely predicted follow-up abundance of F. prausnitzii. The abundance of F. prausnitzii was also inversely correlated with adiposity indicators. FMT from corticosterone-induced obese mice to antibiotic-treated recipients successfully recapitulated the obese phenotype. Supplementation with either F. prausnitzii or butyrate in corticosterone-induced obese mice significantly alleviated body fat accumulation, subcutaneous white adipose tissue (sWAT) weight gain, and lean mass reduction. Mechanistically, transcriptome and RT-qPCR analyses revealed that F. prausnitzii exerts its anti-obesity effects by upregulating the expression of genes related to fatty acid metabolism in sWAT. An in vitro model further confirmed that fatty acid metabolism contributes to butyrate-mediated protection against chronic stress-induced obesity.

CONCLUSION

These findings suggest that F.prausnitzii and butyrate may prevent obesity related to psychological stress through mechanisms involving fatty acid metabolism.