Bifidobacterium animalis subsp. lactis C-2 Alleviates DSS-induced Ulcerative Colitis via the Microbiota-tryptophan...

Inflammatory bowel disease (IBD) is a chronic intestinal disorder closely linked to gut microbiota dysbiosis and metabolic disturbances. This study investigated the alleviating effects and mechanisms of Bifidobacterium animalis subsp. lactis C-2 (C-2) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) in mice. The results demonstrated that C-2 significantly ameliorated pathological phenotypes in DSS-induced UC mice, including reduced weight loss, lowered disease activity index (DAI) scores, restored colon length, and diminished inflammatory damage of colonic tissue. Meanwhile, C-2 effectively repaired the intestinal barrier by enhancing the expression of tight junction proteins (Claudin-1, Occludin, ZO-1) and MUC2, thereby reducing lipopolysaccharide in serum and rebalancing pro-inflammatory (TNF-α, IL-6, IL-1β) and anti-inflammatory (IL-10) cytokines in the colon and serum. Notably, C-2 reshaped the gut microbiota structure, significantly increasing microbial diversity (Shannon index) and enriching beneficial bacteria such as Bifidobacterium and Prevotellaceae. Metabolomic analysis further revealed that C-2 modulated the gut tryptophan metabolism pathway, influencing the levels of tryptophan-derived indole metabolites including indole-3-propionic acid (IPA) and indole-3-acrylic acid (I3A), which were associated with activation of the aryl hydrocarbon receptor (AhR)/Cyp1a1 signaling pathway to enhance barrier integrity and suppress inflammation. Moreover, C-2 intervention restored short-chain fatty acids (SCFAs) levels. In summary, C-2 alleviates UC in mice through synergistic mechanisms including optimizing gut microbiota composition, boosting SCFA production, and enhancing tryptophan-derived metabolites. Collectively, these findings support the potential of C-2 as a candidate probiotic intervention strategy for IBD.