P0555Plasma Metabolomic and Lipidomic Profiling Reveals Distinct Molecular Signatures and Time-Dependent Remodeling in Ulcerative Colitis

Abstract Background Ulcerative colitis (UC) is a chronic inflammatory bowel disease marked by relapsing mucosal inflammation. Recent data indicate that subclinical metabolic and immune 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 remodelling in UC. Methods Plasma samples from 58 UC patients in clinical remission and 70 age- and sex-matched healthy controls (HC) were analysed 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 (p 0.05), were applied, and pathway enrichment was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Overall, 128 individuals were included, and age, sex, body mass index, smoking status and serum lipid measurements were similar between groups. Untargeted GC–MS identified 140 metabolites, with PLS-DA showing clear separation. Fifteen metabolites differed significantly, with lower β-alanine, lactic acid, pyruvic acid and saturated fatty acids, and higher N2-(D-1-carboxyethyl)-L-arginine, D-erythrose-4-phosphate and 2-hydroxybutyric acid. Pathway analysis indicated changes in cofactor biosynthesis, propanoate metabolism, fatty-acid biosynthesis and amino-acid biosynthesis. Lipidomic profiling showed 126 altered species across phosphatidylcholines, lysophosphatidylcholines, phosphatidylethanolamines, oxidised phospholipids, sphingomyelins, diacylglycerols, triglycerides and fatty acids. Stratification by disease duration (≤2 vs 2 years) revealed distinct metabolic patterns. Altered pathways involved alanine, aspartate, glutamate, glycine–serine–threonine and cysteine–methionine metabolism, branched-chain amino-acid biosynthesis and purine, pyrimidine and 2-oxocarboxylic-acid metabolism. Several amino acids (L-alanine, glutamine, serine, methionine) were higher in early disease, whereas leucine was lower. Longer disease duration showed higher sphingomyelins and diacylglycerols, triglyceride species variation and increased phosphatidylcholine composition. Conclusion UC remains metabolically active even during remission. This study reveals persistent metabolite and lipid alterations that evolve with disease duration, highlighting ongoing biological activity beyond mucosal healing. These time-dependent changes may help identify metabolic biomarkers for monitoring and guide personalised therapeutic strategies. Conflict of interest: Ms. Bilican, Gülden: No conflict of interest Noor, Nurulamin M.: Dr Noor has received educational grants and/or speaker fees from AbbVie, BMS, Celltrion, Dr Falk, Ferring, J&J, Lilly, Medfyle, Pfizer, Pharmacosmos, Takeda and Tillotts Haas, Stephan L.: SLH served as a speaker and/or advisory board member for Celltrion, Ferring, Janssen, Lilly, Mediahuset, Pfizer, Santax Medico, Takeda, and Tillotts Pharma. Petrousis, Grigorios: No conflict of interest Koçak, Engin: No conflict of interest Karakan, Tarkan: No conflict of interest