URINE METABOLITES CHARACTERIZE THE INFLAMMATORY BOWEL DISEASE

MARIA EMILIA CUENCAS BARRIENTOS; LEONELLA TANTUCCI; DAFNE CABRERA; MARINA LAURA FERNANDEZ; ADRIANA FOCHESATO; ANDREA DELGADO; CORREA SILVIA; BALDERRAMO, DOMINGO; ROMAGNOLI, PABLO ALBERTO

San Luis

Congreso; Reunion Anual Sociedad Argentina de Inmunologia 2023; 2023

Sociedad Argentina de Inmunologia

Introduction:Inflammatory Bowel Disease (IBD), which comprises Crohn´s Disease (CD) and Ulcerative Colitis (UC), is a disorder in which complex interactions between genetic, environmental, and microbial factors trigger alterations in the immune responses of the intestinal mucosa that result in chronic intestinal inflammation. On the other hand, nutrient catabolism from the diet carried out by the microbiota results in the formation of metabolites that also impact immune responses on the intestinal mucosa. Considering that IBD patients have altered microbiota compared to healthy individuals and that the urinary metabolic profile of an individual is the result of a combination of genetic, dietary, and microbial components, we propose the hypothesis that the urinary metabolic profile distinguishes people with IBD from healthy individuals. Objective: To perform a metabolomic analysis of urine samples from healthy individuals and patients with IBD.Methods: In this study, 27 patients were divided into control (n=10), UC (n=10), and CD (n=7) groups. The activity of IBD in patients was clinically estimated using the Mayo score (UC) or the Harvey-Bradshaw index (CD). Metabolites in urine were measured using gas chromatography-mass spectrometry (GC-MS). Metabolomic analysis and machine learning were performed using the MetaboAnalyst software. Samples were normalized by sum without data transformation and with autoscaling. PLS-DA was used for multivariate analysis, and clustering separation was performed using hierarchical clustering. To identify and interpret patterns of metabolite concentration changes in a biologically meaningful way we perform Over Representation Analysis (ORA). The statistical analysis included Shapiro-Wilk test for data normality, one-way ANOVA with post-hoc analysis using the Tukey method for group comparison, and Pearson correlation for measuring correlation between values. Results: In total, 62 organic acids were detected. Comparing UC and control subjects revealed 11 significantly altered metabolites (9 increased and 2 decreased). Increased metabolites comprised lactic acid (p=0.0015), pyroglutamic acid (p=0.0147), isocitric acid (p=0.0325), and phosphoric acid (p=0.0091), whereas comparing CD and control subjects revealed only 2 significantly altered metabolites, glycolic acid (p=0.0214), and lactic acid (p=0.0111). Interestingly, the value of lactic acid varies with the stage of UC, being more concentrated in patients in remission. The most affected metabolic pathways are related to energy metabolism and oxidative stress, including the warburg effect (p=0.0016), gluconeogenesis (p=0.0106), pyruvate metabolism (p=0.0197) and glutathione metabolism (p=0.0039). Conclusion: We found that the urinary metabolic profile of IBD patients differs from the control group, particularly for UC patients. These metabolites could be used as indicators to improve the diagnosis, monitoring, and treatment of patients with IBD.