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Background Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder closely associated with gut microbiota dysbiosis and disruption of intestinal epithelial homeostasis. Blautia producta (B. producta), an important gut commensal, may exert protective effects against colitis; however, its key functional metabolites and underlying mechanisms remain unclear. This study aimed to determine the protective role of B. producta in DSS-induced colitis and to identify its key metabolite and downstream molecular mechanism.Methods A DSS-induced mouse colitis model and DSS-induced intestinal epithelial inflammatory cell model were established to evaluate the effects of B. producta on colitis-related phenotypes, gut microbial structure, and epithelial barrier function. Live bacteria, heat-inactivated bacteria, and culture supernatant were compared, and enzymatic pretreatment together with ultrafiltration of the supernatant was used to identify the active fraction. Non-targeted metabolomics of bacterial supernatant and mouse feces, together with targeted tryptophan metabolomics, were integrated to identify key functional metabolites. RNA sequencing, enrichment analysis, correlation analysis, and molecular assays were performed to explore downstream mechanisms.Results B. producta significantly alleviated DSS-induced body weight loss, increased disease activity index, colon shortening, and histological injury, while restoring tight junction proteins and MUC2 expression (IDDF2026-ABS-0524 Figure 1. B. producta alleviates intestinal inflammation and restores the intestinal mucosal barrier in mice). Metagenomic analysis showed that B. producta markedly reshaped the gut microbial structure in colitis mice. In vitro, B. producta culture supernatant exhibited stronger protective effects than live or heat-inactivated bacteria, and its activity was mainly associated with low-molecular-weight fractions (IDDF2026-ABS-0524 Figure 2. The functional substance by which B. producta improves intestinal homeostasis is present in its culture supernatant). Integrated metabolomics identified indole-3-lactic acid (ILA) as a key candidate metabolite (IDDF2026-ABS-0524 Figure 3. The functional substance by which B. producta improves intestinal homeostasis is present in its culture supernatant). ILA markedly attenuated DSS-induced inflammatory injury and improved epithelial barrier function (IDDF2026-ABS-0524 Figure 4. ILA alleviates intestinal inflammation and restores the intestinal mechanical barrier in colitis mice). RNA-seq revealed that ILA-responsive genes were mainly enriched in the PPAR signaling pathway, as well as lipid metabolism- and ketone metabolism-related pathways, with significant upregulation of HMGCS2 and other key molecules (IDDF2026-ABS-0524 Figure 5. ILA alters the gene expression profile in colitis mice and activates the PPAR signaling pathway). Correlation analysis further showed that PPAR pathway-related genes were positively associated with barrier-repair markers and negatively associated with inflammatory factors.Conclusions B. producta ameliorates DSS-induced colitis through secretion of the key metabolite ILA. Its protective effects are likely mediated by activation of the PPAR/HMGCS2-associated metabolic axis, restoration of intestinal epithelial homeostasis, and suppression of inflammation. These findings provide experimental evidence supporting microbiota- and metabolite-based therapeutic strategies for IBD.Abstract IDDF2026-ABS-0524 Figure 1Abstract IDDF2026-ABS-0524 Figure 2Abstract IDDF2026-ABS-0524 Figure 3Abstract IDDF2026-ABS-0524 Figure 4Abstract IDDF2026-ABS-0524 Figure 5