Urinary Organic Acid Profiling by GC-MS Reveals Distinct Metabolic Signatures for Non-Invasive Diagnosis and Disease Activity Monitoring of Inflammatory Bowel Disease

Abstract

Inflammatory bowel disease (IBD) prevalence is rising rapidly in South America, yet non-invasive diagnostic and monitoring strategies remain inadequate. Urine samples from 30 individuals (10 healthy controls [C], 10 ulcerative colitis [UC] and 10 Crohn’s disease [CD] patients) from a South American cohort were analyzed by gas chromatography–mass spectrometry (GC-MS); metabolomic profiling employed multivariate statistics, pathway enrichment analysis, and receiver operating characteristic (ROC) curve analysis. Profiling of 62 organic acids revealed distinct metabolic patterns across groups: UC patients showed significantly elevated lactic, adipic, glutaric, phosphoric, aconitic, palmitic, 2-hydroxyisobutyric, pyroglutamic, phthalic, azelaic, and glycolic acids relative to controls, with reduced 4-hydroxyphenyllactic acid and trends toward reduction of 3-(3-hydroxyphenyl)propionic and 3-hydroxyphenylacetic acids; CD patients showed elevated 2-hydroxyisovaleric acid. Lactic, glutaric, and palmitic acids were associated with active UC, while glycolic, phosphoric, and adipic acids characterized remission. Pathway analyses indicated alterations in energy and amino acid metabolism. Exploratory multivariate ROC analyses yielded area under the Curve (AUC) values of 0.754 (IBD vs. controls), 0.904 (UC vs. controls), 0.798 (CD vs. controls), and 0.764 (UC vs. CD). These findings identify candidate urinary organic acid biomarkers associated with IBD status and UC disease activity, warranting validation in larger, independent, longitudinal cohorts before non-invasive tools for disease stratification and personalized management of UC and CD can be developed.