This study aimed to characterize the alterations in both oral and gut microbiota in a mouse model of depression and to explore their potential role in the pathogenesis of major depressive disorder (MDD) through the oral-gut-brain axis. A depression model was established in male C57BL/6J mice using chronic social defeat stress (CSDS) paradigm. Depressive phenotypes were confirmed through social interaction, sucrose preference, open field, tail suspension, and forced swim tests. The microbial composition of oral and gut samples was analyzed using 16S rRNA sequencing, with Linear Discriminant Analysis Effect Size (LEfSe) employed to identify differentially abundant taxa and Spearman correlation analysis to examine microbiota-behavior relationships. CSDS successfully induced robust depression-like behaviors, including social avoidance, anhedonia, and behavioral despair. Beta-diversity analysis revealed significant separation in oral microbiota between CSDS and control groups. LEfSe analysis identified distinct microbial signatures: control mice were enriched in oral Streptococcus and gut commensals including Lachnospiraceae, Bacteroides and Oscillospiraceae, whereas CSDS mice showed expansion of oral Muribacter and Rodentibacter and gut Alloprevotella, Helicobacter and Colidextribacter. Correlation analyses demonstrated significant associations between specific microbial patterns and depression-like behaviors, with control-enriched taxa negatively correlating with behavioral deficits. Furthermore, significant cross-habitat microbial correlations were observed between oral and gut differential taxa. Our findings demonstrate that CSDS induces divergent microbial alterations in both oral and gut ecosystems, which are systematically associated with depression-like behaviors. These results provide compelling evidence for the involvement of the oral-gut-brain axis in depression pathophysiology and suggest that modulating these microbial ecosystems may represent a potential therapeutic strategy for MDD.
Gut-Brain Axis