Lacticaseibacillus rhamnosus LRa05 Mitigates DSS-Induced Colitis via Boosting Beneficial Gut Microbiota and Facilitating CD4⁺Foxp3⁺ Treg Differentiation

Background Lacticaseibacillus rhamnosus LRa05, originally isolated from infant feces, has been widely used as a probiotic in the food industry. However, its potential as an orally administered probiotic therapeutic for inflammatory bowel disease (IBD) remains underexplored, particularly from an immune regulatory perspective. Results In this study, we demonstrated that administration of LRa05 conferred protective effects in a DSS-induced colitis mouse model. Such protective effects were reflected by attenuated weight loss, preserved colon length, reduced spleen index, and diminished histopathological damage in the colon. Mechanistically, while LRa05 administration exerted minimal impact on the overall microbiota diversity, it altered the species composition. Notably, the abundance of the beneficial bacterium Akkermansia muciniphila was 10-fold higher in LRa05 treated mice compared to controls. This change was thought to further modulate microbial metabolic pathways. More importantly, LRa05 promoted the expansion of CD4⁺Foxp3⁺ Treg cells, as evidenced by a remarkable increase in Treg frequency in both the spleen and mesenteric lymph nodes. Consequently, proinflammatory cytokine levels were reduced, thereby excessive colonic inflammation was suppressed. Conclusions Taken together, our findings identify LRa05 as a potential therapeutic agent for DSS-induced colitis, with its protective effects mediated through enhancing beneficial gut microbiota and facilitating Treg cell differentiation.