Weissella confusa RY-1 ameliorates DSS-induced colitis by restoring intestinal barrier, modulating gut microbiota, and reprogramming microbial metabolism.

Ulcerative colitis (UC) remains a challenging chronic inflammatory bowel disease with limited treatment options. This study investigates the protective role of Weissella confusa RY-1, a potential probiotic strain isolated from human gastric fluid, in a dextran sulfate sodium (DSS)-induced murine colitis model. Administration of W. confusa RY-1 significantly ameliorated colitis symptoms in mice subjected to a 10-day colitis induction model, as demonstrated by improved body weight recovery, reduced disease activity index (DAI) scores, attenuated colon shortening, and restored colonic histoarchitecture. The probiotic treatment enhanced intestinal barrier integrity through upregulation of tight junction proteins ZO-1 and Occludin. 16S rRNA sequencing revealed substantial modulation of gut microbiota, characterized by reduced abundance of pro-inflammatory Escherichia-Shigella and enrichment of beneficial Akkermansia. Metabolomic analysis further demonstrated metabolic reshaping with elevated anti-inflammatory linoleic acid and decreased succinic acid levels. These findings collectively indicate that W. confusa RY-1 exerts protective effects against colitis through multiple mechanisms including barrier reinforcement, microbiota modulation, and metabolic reprogramming, suggesting its promising potential as a novel probiotic-based intervention for ulcerative colitis.