Abstract Background and aims There is growing evidence that metabolomics can help identify molecular mechanisms underlying inflammatory bowel disease (IBD) by characterizing metabolic alterations occurring during the preclinical phase. This project aims to conduct the largest metabolomic study of pre-diagnostic IBD to date, providing a comprehensive characterization of molecular processes preceding clinical onset. Methods A major bottleneck in studying pre-diagnostic IBD is access to appropriate biological samples. By leveraging the unique combination of population-based biobanking within the Danish National Biobank and linkage to nationwide health registers, we will assemble a large cohort of individuals with available pre-diagnostic serum samples and matching controls (N = 1,000). Untargeted metabolomic profiling of both lipid and polar fractions will enable wide coverage of the pre-diagnostic metabolome. Machine learning approaches will be applied to develop predictive models and to identify metabolite patterns associated with disease outcomes, contrasting individuals who develop IBD with representative controls who remain disease-free. Anticipated impact We aim to identify novel metabolic alterations in the preclinical phase of IBD and determine the temporal onset of these changes by assessing how many years prior to diagnosis of Crohn’s disease (CD) and ulcerative colitis (UC) they are detectable. We will also assess the specificity of these metabolic signatures by comparing them to those observed in other immune-mediated inflammatory diseases, helping to distinguish disease-specific from shared inflammatory processes. In the short term, the findings will provide novel candidate biomarkers and generate hypotheses for new mechanistic insights into IBD development. In the long term, a deeper understanding of early metabolic alterations may open avenues for preventive interventions or targeted therapies aimed at halting disease progression before symptom onset. Ultimately, this work will advance fundamental knowledge of IBD biology and bring us closer to personalized care for IBD.
Filip Ottosson (Thu,) studied this question.