Biomarker signatures in pathophysiology and therapeutic interventions in inflammatory bowel diseases: a multimodal approach

Inflammatory bowel disease (IBD) is a term mainly used to describe two diseases: Crohn’s disease (CD) and ulcerative colitis (UC). These are complex diseases of the gastrointestinal tract, characterised by a relapse-remitting disease course. Hence, IBD is difficult to predict and to adequately treat. Since IBD is a complex, heterogeneous and unpredictable disease, there is an urgent need for biomarkers, which are objectively measured parameters of (ab)normal biological processes or -systems, which may help to (early) diagnose and classify IBD, to assess disease activity and disease complications, and to accurately predict how a patients’ disease course will develop and/or how a patient will respond to a particular treatment. The findings presented in this thesis represent a number of newly identified biomarkers for multiple disease outcomes in patients with IBD. These outcomes included, but were not limited to, diagnosis and classification (Part I), disease activity and complications (Part II and III), and modulation by and prediction of treatment effects (Part IV). This thesis adopted a multimodal approach by exploring biomarkers from different biological perspectives and by performing laboratory-, clinical- and computational research (and combinations thereof). We demonstrated that immune system components (Part I), inflammation, permeability and fibrosis (Part II), and oxidative stress (Part III) provide excellent resources for biomarker discovery and application. The work presented in this thesis sheds light on the establishment of a “systems biology” approach, studying the interplay between multiple disease processes to establish personalised medicine for patients with IBD, thereby improving outcomes of patients with IBD.