Lactobacillus fermentum alleviates DSS-induced ulcerative colitis by protecting the intestinal barrier, inhibiting the inflammatory response, restoring short-chain fatty acids, and regulating intestinal flora and metabolites

Ulcerative colitis , a prevalent chronic inflammatory disease, lacks efficacious treatments with minimal side effects. This study investigated the therapeutic potential of L. fermentum S1, isolated from feline fecal samples, in alleviating dextran sulfate sodium DSS-induced colitis in mice and explored its mechanisms of action. Through a combination of physiological, microbiological, and metabolomic analyses, we demonstrated that L. fermentum S1 significantly mitigated DSS-induced body weight loss, colon shortening, and intestinal barrier dysfunction. The strain enhanced short-chain fatty acid production and modulated gut microbiota composition, increasing beneficial genera (Akkermansia, Ligilactobacillus, Turicibacter, Prevotella_9, and Unclassified_Vicinamibacterales) while suppressing pathogenic taxa (Parabacteroides, Rikenellaceae_RC9_gut_group, Ruminococcus, and [Eubacterium]_fissicatena_group).