Inflammatory bowel disease (IBD) exhibits significant heterogeneity, encompassing variation in affected gastrointestinal segments and disease course, both within and between subtypes. Proteomics and metabolomics may offer insights into the IBD spectrum and serve as a basis for biomarker discovery, thereby addressing healthcare challenges and advanc-ing our understanding of disease mechanisms. The overall aim of this thesis was to investigate proteomics and metabolomics in relation to IBD.

Patient cohorts are the foundation for many observational studies. In study I, we described the Swedish Inception Cohort in IBD (SIC-IBD), which was used for several subsequent studies. Based on serum proteins, we observed colonic Crohn’s disease (CD) as an intermediate subtype between ileal CD and ulcerative colitis (UC) in study II. In study III, we identified mucosal markers associated with an aggressive course of UC (e.g., MMP-1 and OPG) and developed a mucosal protein signature to predict the disease course. Mucosal angiotensin-converting enzyme 2 (ACE2) levels did not differ between IBD and symptomatic or healthy controls in study IV, but levels were higher in inflamed compared to non-inflamed ileal biopsies from patients with CD. In study V, we found metabolites associated with incident paediatric IBD compared with symp-tomatic controls, among these a positive association for aryl sulfate.

In this thesis, we examined serum proteins, mucosal proteins and exposome-related metabolites in IBD. We identified differences between subtypes of IBD, between inflamed versus non-inflamed tissue, as well as between IBD, symptomatic and healthy controls. These results may inform further biomarker research and support a molecular stratification of IBD.