Lactobacillus fermentum Inhibits the Development of Colitis by Regulating the Intestinal Microbiota and Metabolites to Enhance the Intestinal Barrier and Decrease Inflammatory Responses

Ulcerative colitis (UC) is a chronic inflammatory disorder difficult to cure with current treatments. Therefore, preventive interventions for UC are crucial. This research investigated the intervention potential of <i>Lactobacillus (L.</i>) <i>fermentum</i> S1 derived from a cat in reducing dextran sulfate sodium (DSS)-triggered UC. Through a combination of physiological, microbiological, and metabolomic analyses, we demonstrated that preventive supplementation with <i>L. fermentum</i> S1 significantly mitigated DSS-triggered body weight loss, colon shortening, intestinal barrier (IB) dysfunction, and inflammatory reaction. <i>L. fermentum</i> S1 modulated gut microbiota (GM) components and elevated short-chain fatty acids generation. Beneficial genera were abundant (<i>Akkermansia</i>, <i>Ligilactobacillus</i>, <i>Turicibacter</i>, and <i>Prevotella</i>_9) while suppressing pathogenic taxa (Parabacteroides and Acinetobacter). Furthermore, <i>L. fermentum</i> S1 increased the amount of the anti-inflammatory metabolite hecogenin within the intestines. Spearman's correlation analysis exhibited significant associations between microbial shifts and metabolite profiles, suggesting that microbiota-derived metabolites can mediate their therapeutic effects. These outcomes indicate the potential of <i>L. fermentum</i> S1 as a new dietary supplement and provide a theoretical basis for UC prevention.