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Abstract
Background 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.
Methods 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.
Results 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<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)).
Baseline characteristics of included participants
Conclusions 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.