Mucosal Metabolomic Signatures in Chronic Colitis: Novel Insights into the Pathophysiology of Inflammatory Bowel Disease

(1) Background: Inflammatory bowel diseases (IBD) involve complex interactions between genetic factors, aberrant immune activation, and gut microbial dysbiosis. While metabolomic studies have focused on feces and serum, fewer investigations have examined the intestinal mucosa despite its crucial role in metabolite absorption and transport. The current study aimed to identify novel mucosal metabolic pathways that are altered during chronic colitis and to determine microbial contributions to such changes. (2) Methods: The chronic Dextran sulfate sodium (DSS) colitis was induced for five weeks in 7-9-week-old wild-type C57BL/6J male mice followed by microbial profiling with targeted 16srRNA sequencing service. Mucosal metabolite measurements were performed by Metabolon (Morrisville, NC). The data were analyzed using the bioinformatic tools Pathview, MetOrigin, and Metaboanalyst. (3) Results: Our novel findings demonstrated increases in several host- and mi-crobe-derived purine, pyrimidine, endocannabinoid, and ceramide metabolites in colitis. Origin analysis revealed microbial-related tryptophan metabolites kynurenine, anthranilate, 5-hydroxyindoleacetate, and C-glycosyltryptophan were significantly increased in colon mucosa during chronic inflammation and strongly correlated with disease activity. (4) Conclusions: These findings offer new insights into the pathophysiology of IBD and provide novel potential targets for microbial-based therapeutics.