<em>Lactiplantibacillus plantarum</em> LP-315 ameliorates DSS-induced colitis in mice by regulating gut microbiota and metabolites

Ulcerative colitis is a globally prevalent chronic disease that continues to attract significant attention. 5-aminosalicylicacid (5-ASA) is the primary treatment for mild to moderate colitis, but its use may be compromised by side effects and dependency. <em>Lactiplantibacillus </em>(<em>L</em>.)<em> plantarum</em> has shown promise as a remission strategy for alleviating colitis. Our previous study demonstrated that supplementation with <em>L</em>. <em>plantarum</em> LP-315 (LP-315) effectively alleviated dextran sulfate sodium (DSS)-induced colitis in mice, though its effects on the gut microbiota and metabolism remained unexplored. In this follow-up study, we analyzed the fecal metagenome, gut metabolic modules (GMMs), and bioactive metabolites in four groups of mice (n = 8 per group): normal control group, DSS group, LP group (LP-315 intervention), and ME group (5-ASA intervention). A correlation network analysis was performed to investigate the associations between key differential gut microbial species, GMMs, metabolites, and the significantly improved phenotypic indicators identified in previous study. The results revealed that LP-315 ameliorated colitis symptoms by modulating the gut microbiota (increasing <em>Duncaniella newyorkensis</em>), bioactive metabolites (reducing serotonin, while increasing indole-3-acetic acid, xanthurenic acid, and indole-3-carboxylic acid), and the inflammation-associated Glutamine degradation pathway. Compared to 5-ASA, which primarily reduced the abundance of the harmful bacterium <em>Parasutterella excrementihominis</em>, LP-315 exhibited superior efficacy in ameliorating DSS-induced colitis symptoms. Besides, 25 bacterial species and 14 GMMs, closely linked to colitis but unchanged by the intervention, were identified as worthy of further targeted investigation. These findings provide rigorous preclinical evidence supporting the potential and feasibility of <em>L. plantarum </em>in colitis amelioration.