In this study, we explored how gut microbiota, intestinal barrier function, and inflammation are connected to social behavior. We compared stress-resilient Dominant mice with stress-vulnerable Submissive mice and evaluated gut microbiome composition, gut permeability, immune markers, short-chain fatty acids, and behavior.

We found that Submissive mice showed early-life gut microbiome alterations, reduced beneficial bacteria, increased gut permeability, lower short-chain fatty acid levels, reduced regulatory T cells, and impaired social behavior. We then evaluated whether improving gut barrier function and reducing inflammation could reverse these effects. Hyaluronic acid improved gut permeability, colon length, and social behavior, while celecoxib improved sociability and reduced depressive- and anxiety-like behaviors.

Together, our findings suggest that improving intestinal health may help restore social behavior through the gut–brain axis.