14 Abstract Inflammatory bowel diseases (IBD), encompassing Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the gastrointestinal tract. Patients with IBD experience alternating episodes of active and quiescent disease, which vary greatly and are difficult to treat. Currently, there is no cure for IBD and its exact pathogenesis remains incompletely understood. IBD is a complex, heterogeneous and unpredictable condition, which not only complicates its early detection and diagnosis, but also the prediction of disease course and response to therapy. This emphasizes the urgent need for biomarkers, which are objectively measured indicators of (ab)normal biological processes or – systems. In the context of IBD, biomarkers are crucial for a variety of purposes, including (early) diagnosis, assessment of disease activity and complications, and prediction of therapeutic response, disease course and prognosis. This thesis aims to identify and apply novel biomarkers in patients with IBD, while simultaneously evaluating their utility to predict clinically relevant outcomes (e.g. disease activity and therapeutic response) and their amenability to nutritional and drug-based interventions. For that purpose, biomarkers are explored from different biological systems and -mechanisms, including (antimicrobial) immunity (Part I), inflammation and fibrosis (Part II), and oxidative stress (Part III). Subsequently, the utility and dynamics of several of these biomarkers are assessed in relation to nutritional and drug-based interventions (Part IV). Simultaneously, this thesis also aims to deepen our understanding of the complex interactions of pathophysiological factors underlying the pathogenesis of IBD. Finally, the scientific and clinical sequelae of the recent coronavirus disease 2019 (COVID-19) pandemic are discussed in the context of biomarkers and IBD (Part V). Ultimately, this thesis aims to contribute to the characterisation and validation of novel biomarker signatures in patients with IBD by adopting a multimodal approach, consisting of multiple biological systems and -mechanisms and a combination of in vitro, in vivo and in silico strategies to interrogate them. Chapter 1
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