P439 Mild Crohn’s disease is characterized by a unique serum metabolomic signature

Abstract Background Approximately 20-30% of patients with Crohn's disease (CD) experience a mild disease course following initial diagnosis. Balancing the effectiveness and safety of medical treatments is crucial in the management of mild CD. However, the main clinical challenge currently lies in identifying patients likely to maintain this mild disease course, underscoring the urgent need for biomarkers of mild CD. In this study, we therefore aimed to identify potential circulating biomarkers for patients with mild CD leveraging a metabolomics approach. Methods Patients with mild CD were retrospectively identified from participants of the Mount Sinai Crohn's and Colitis Registry (MSSCR). Baseline screenings in MSSCR included assessments of the use of biologicals and immunomodulators, history of IBD-related surgeries, and the presence of disease complications (including stricturing, penetrating, and perianal CD). Mild CD was defined as the absence of all these variables at baseline as well as after a 5-year follow-up period. Untargeted serum metabolomic profiling was performed to measure the circulating metabolome of these patients. Multivariable logistic regression analyses, adjusting for age, sex, measurement batch, and smoking behavior, were conducted to identify metabolites associated with mild CD. Results In total, 114 patients with CD were characterized in which 1,456 different metabolites were profiled, with 32 patients (28.1%) meeting the criteria for mild CD. The remaining 82 patients (71.9%) partially met criteria for mild CD; these were all biologic-naïve and did not undergo IBD-related surgeries. Multivariable logistic regression revealed 45 distinct metabolites that were significantly associated with the mild CD group (nominal P<0.05). Sphingomyelin compounds and ceramides exhibited the most prominent associations with mild CD (odds ratios [OR] all >2.0), while tryptophan, pantothenate, and salicylate metabolites were also linked to mild CD. Conversely, primary and secondary bile acid metabolites and amino acid derivatives from lysine-, tyrosine-, and proline metabolism were all inversely associated with mild CD. Conclusion Mild CD is associated with distinct alterations in metabolic pathways compared to patients with moderate-to-severe CD. Future research should focus on longitudinal assessments of these metabolites for disease monitoring and determining optimal therapeutic strategies for this clinical subgroup.