Plasma metabolomic and lipidomic profiling reveals distinct molecular signatures and time-dependent remodeling in ulcerative colitis

Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by relapsing mucosal inflammation. Recent data indicate that subclinical metabolic disturbances persist even in patients who have achieved remission. However, the temporal evolution of these molecular alterations remains poorly defined. This study examined how disease duration shapes systemic metabolic and lipidomic remodeling in UC. Plasma samples from 58 UC patients in clinical remission and 70 age- and sex- matched healthy controls (HC) were analyzed using integrated untargeted gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS). Patients were stratified by disease duration (≤ 2 years vs. > 2 years). Multivariate and univariate analyses, including partial least squares discriminant analysis (PLS-DA), variable importance in projection (VIP) scoring, and t-tests or Mann–Whitney U test (p < 0.05), were applied, and pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. UC patients showed distinct plasma metabolomic and lipidomic signatures compared with HC, with 15 metabolites and 126 lipid species significantly altered. Reduced pyruvic and lactic acids, together with disrupted fatty-acid and amino-acid metabolism, suggested impaired energy and redox homeostasis. Lipidomic profiling revealed broad disturbances across phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamines, sphingomyelins, diacylglycerols, and triglycerides, reflecting persistent oxidative and inflammatory imbalance. Stratification by disease duration revealed progressive remodeling, particularly within amino-acid pathways and sphingolipid metabolism. Even during remission, UC exhibits systemic metabolic disequilibrium that evolves with disease chronicity. These time-dependent changes could guide the identification of metabolic biomarkers for disease monitoring and personalized therapeutic strategies. Ulcerative colitis is associated with metabolic and lipidomic alterations, but it is unclear whether these changes persist during clinical remission and how they evolve over the course of the disease. This study highlights persistent metabolic pathway alterations in ulcerative colitis during remission, driven by disease duration. Understanding that ulcerative colitis may exhibit persistent molecular alterations despite clinical remission may help clinicians better interpret remission, identify patients at risk of chronic disease burden, and move toward more personalized monitoring strategies.