IDDF2024-ABS-0387 Fecal metabolites predict the therapeutic effect of 5-ASA in patients with ulcerative colitis

<h3>Background</h3> 5-aminosalicylate acid (5-ASA) is the first-line therapy for mild to moderate ulcerative colitis (UC). However, up to 56% of patients on 5-ASA treatment could not achieve mucosal healing, which is the therapeutic target of UC. At present, predictors for patients’ response to 5-ASA are lacking. Our aim was to identify fecal metabolite markers to predict the therapeutic effect of 5-ASA in patients with UC. <h3>Methods</h3> Stool samples were collected from patients with active UC at baseline and analyzed using the untargeted metabolomics analysis. Effective therapy was defined as achieving clinical remission within 8 weeks or mucosal healing within 1 year of 5-ASA treatment. Orthogonal Projections to Latent Structures Discriminant Analyses (OPLS-DA) were implemented to correlate patient groups to fecal metabolites in linear multivariate models. The Lasso regression model was constructed to predict ineffective 5-ASA therapy in UC patients. <h3>Results</h3> Among the 30 UC patients involved (median age 37 years old, men 50%), 15 patients belonged to the effective group and the ineffective group, respectively (IDDF2024-ABS-0387 Table 1). The relative abundances of carbohydrates, phenols, and amines in the feces of the two patient groups are significantly different (IDDF2024-ABS-0387 Figure 1 (A)). In OPLS-DA analysis, fecal metabolites could distinguish the patients who did not respond well to 5-ASA treatment (IDDF2024-ABS-0387 Figure 1 (B)). There are 11 metabolites up-regulated and 1 metabolite down-regulated in the ineffective group (P&lt;0.05) (IDDF2024-ABS-0387 Figure 1 (C)). These differential metabolites are significantly enriched in the biosynthesis and degradation of lysine, pyruvate metabolism as well as the pentose phosphate pathway (IDDF2024-ABS-0387 Figure 1 (D)). The Lasso regression was conducted to identify the fecal metabolites predicting 5-ASA inefficacy; they were N(alpha)-Acetyl-L-lysine, tyramine, and pyruvic acid, which presented a high prediction value (AUC=0.929, p=0.002, sensitivity=93.3%, specificity=86.7%) (IDDF2024-ABS-0387 Figure 1 (E,F)). <h3>Conclusions</h3> We identified several fecal metabolites associated with the therapeutic effect of 5-ASA. A panel composed of fecal N(alpha)-acetyl-L-lysine, tyramine, and pyruvic acid may be promising for predicting patients’ response to 5-ASA therapy.