Protective effect of yak yogurt derived Lactiplantibacillus plantarum DACNJS22 fermented milk on DSS-induced colitis: Insights from in vitro and in vivo studies.

Probiotic fermented milk has garnered significant attention as a functional food owing to its health-promoting effects. This study aimed to evaluate the in vitro probiotic characteristics of Lactiplantibacillus plantarum DACNJS22 (S22), a strain isolated from yak yogurt and elucidate the metabolic profile of its fermented milk and its protective effects against dextran sulfate sodium (DSS)-induced colitis. Phenotypic and whole-genome sequencing analyses confirmed that S22 possesses a favorable safety profile and exhibits a broad spectrum of probiotic properties, including strong antimicrobial activity, resilience to acidic and bile salt conditions, adhesion to intestinal epithelial cells, and potent immunomodulatory and anti-inflammatory effects. Furthermore, milk fermentation by S22 altered the metabolite profiles of the samples, which was predicted to alleviate colitis by regulating the inflammatory response through network pharmacological analysis. Notably, in vivo experiments demonstrated that S22-fermented milk effectively alleviated DSS-induced colitis, restored histopathological damage, reduced inflammatory cytokine levels, and promoted colonic expression of tight junction proteins. Additionally, S22-fermented milk ameliorated gut microbial dysbiosis by enriching beneficial microorganisms and promoting short-chain fatty acid production. Overall, these findings suggest that the targeted development of probiotic-fermented milk with prebiotic properties is a promising strategy for promoting gut health and maintaining intestinal homeostasis.