Decoding the Protective Mechanisms ofFermented Juice against CUMS-Induced Depression-like Behaviors: Insights from Gut Microbiota and Neuroinflammation.

Abstract

Depression, recognized for its complex pathophysiology, remains a prevalent psychiatric disorder. The gut-brain axis is increasingly implicated in the pathophysiology of depressive symptoms, highlighting it as a promising intervention target. This study evaluated the protective effects offermented juice (RRFJ) in a chronic unpredictable mild stress (CUMS) mouse model. Results showed that RRFJ pretreatment significantly mitigated CUMS-induced depressive-like behaviors and hippocampal damage in C57BL/6J mice. Mechanistic investigations revealed that RRFJ induced remodeling of the gut microbiota characterized by an increased Firmicutes-to-Bacteroidetes ratio. This enhanced intestinal barrier integrity by reducing gut-derived lipopolysaccharide and upregulating tight junction proteins, ultimately resulting in decreased neuroinflammation in the hippocampus. Furthermore, RRFJ pretreatment modulated host metabolic profiles in plasma and brain tissue. In conclusion, RRFJ mitigates depressive-like behaviors, highlighting its preventive potential via mechanisms, including gut microbiota modulation, neuroinflammation suppression, and metabolic shifts in both plasma and brain.