21 of their potential anti-inflammatory, antioxidant or gut microbiota-modulating properties, which should ideally be investigated in both in vitro and in vivo research settings. Besides, there is a need for prospective clinical trials evaluating the efficacy of complete diets or dietary patterns, since all nutrients that we consume may behave differently as part of our total habitual dietary intake, e.g. they may act synergistically or antagonistically with each other. It is important to assess the efficacy of nutritional interventions in IBD and compare this to the existing drug-based therapeutic armamentarium. The importance of a well-established data- and biobank infrastructure In the quest for novel biomarkers for a heterogeneous disease like IBD, it is crucial to make use of well-documented, deeply phenotyped patient- and control cohorts in order to allow detailed phenotypic patient stratification. Although a systems biology approach of IBD is increasingly advocated for the identification of disease biomarkers and therapeutic targets, a major challenge is posed by the fact that cohort characteristics and/or interindividual patient differences frequently explain the majority of biomarker variation.70,71 In order to address this issue, it is critical to carefully assess phenotypic characteristics of patients, including demographic, clinical, disease-specific, dietary, and environmental factors. This allows an integrative study of biomarker behaviour and may provide rationale for stratification based on specific phenotypic factors that are relevant to a particular study. The majority of the studies presented in this thesis have been conducted using data and biomaterials thatwerecollectedwithinvarious cohorts andbiobanks. In total, ninedifferent cohorts and biobanks have been used or were newly established as part of my doctoral research (Table 1). The most frequently used cohorts in this thesis include the 1000IBD cohort and the Dutch IBD Biobank. The 1000IBD cohort, or‘1000IBDproject’, is a cohort consisting of patients with IBD treated in the University Medical Centre Groningen (UMCG), of which detailed phenotypic information and several multi-omics profiles have been collected for over 1,000 patients. It features a wealth of biological data including genetics (whole-exome sequencing [WES], genome-wide genotyping [global screening array, GSA]), gene expression (bulk RNA-sequencing of intestinal biopsies), the gut microbiome (fecal metagenomics, 16S rRNA gene sequencing of intestinal biopsies), the plasma proteome (proteomics of plasma inflammation-related proteins) and fecal metabolome (metabolomics), humoral immunity (phage-display immunoprecipitation sequencing, PhIPseq, generating antibody epitope repertoires), but also detailed phenotypic and lifestyle data.72 Different subsets have been used from the Dutch IBD Biobank, which constitutes a prospective, nationwide biobank of patients with IBD who are treated in one of the eight Dutch university medical centres.73 For the establishment of this biobank, a new national institute was founded by the Dutch Federation of University Medical Centres (NFU) to facilitate its logistic infrastructure, referred to as the ‘String of Pearls initiative’ (Dutch: ‘Parelsnoer Instituut’, abbreviated as PSI).74 Using this biobank infrastructure, and together with two fellow PhD-students, I established two unique, specialized cohorts consisting of patients with IBD who received induction therapy with the biologicals infliximab or vedolizumab, who were extensively phenotyped and had biomaterials (serum/plasma) available for biomarker analysis before and during therapy. Furthermore, we performed a study in which data and biomaterials were prospectively collected frompatients with General introduction and outline of the thesis
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