27 PART IV: EVALUATING THERAPEUTIC EFFECTS ON BIOMARKERS IN IBD In Part IV of this thesis, we zoom in on the effects of therapeutic interventions, consisting of nutritional interventions and treatment with biological therapies. First, we focus on the therapeutic effects of single food ingredients in patients with IBD and in healthy volunteers, including vitamin B2 (riboflavin), vitamin C (ascorbic acid), and dietary fibres (inulin-type fructans). In these studies, therapeutic effects are assessed in relation to a number of relevant outcome parameters, including many parameters that were explored earlier in this thesis, e.g. markers of inflammation, oxidative stress and the gut microbiota. In Chapter 19, we start with examining prebiotic modulation of the gut commensal bacterium Faecalibacterium prausnitzii, of which a decreased abundance is associated with IBD and which is often considered as a microbial biomarker for gut health.83,84 Using an in vitro co-culture system (called the ‘Humanoxygen Bacteria-anaerobic’ system, abbreviated as ‘HoxBan’)85, we supplemented dietary fibres, including inulin-type fructans, to F. prausnitzii and analysed the effects of its resulting metabolites (e.g. butyrate and fructose) on gene expression and viability of intestinal epithelial cells (e.g. inflammation- and oxidative stress-marker expression). In Chapters 20 and 21, we evaluated the in vivo effects of riboflavin (vitamin B2) and vitamin C supplementation on systemic oxidative stress and on gut microbiota composition in healthy volunteers, respectively. In Chapter 22, we subsequently tested the effect of riboflavin supplementation on the gut microbiota composition, while simultaneously assessing changes in multiple inflammatory- and oxidative stress biomarkers, in patients with CD (referred to as the ‘RISE-UP’ clinical trial). In this study, we hypothesised that riboflavin supplementation may lead to a reduction in clinical symptoms through beneficial modulation of the gut microbiota composition (specifically by increasing F. prausnitzii abundance), reducing oxidative stress and inflammation, and alleviating CD-specific symptoms (as evaluated by clinical scores and quality of life (QoL) parameters). Second, we explore the potential of biomarkers of inflammation, oxidative stress, fibrosis and iron status to predict response to biological therapy in patients with IBD, focusing on IFX and VEDO induction therapy. In addition, we aimed to study the changes of these biomarkers upon treatment with these biologicals in order to gain insight into the dynamics of the pathophysiological processes that these biomarkers represent. In Chapter 23, we assess the early effects of IFX and VEDO induction therapy on markers of systemic iron status in patients with IBD, and evaluated their diagnostic capacity in relation to iron deficiency, that may in turn lead to anaemia in these patients, which is a common extraintestinal manifestation. Further, we study the relationships between systemic iron indices and markers of inflammation, oxidative stress and hypoxia in patients with active IBD. In Chapters 24 and 25, we continue studying the effects of IFX and VEDO induction therapy, but then focus on markers of fibrosis and collagen remodelling. In these studies, we aimed to assess the potential of biomarkers of collagen formation and degradation in monitoring and/or predicting response to these biological therapies in patients with CD, since CD is particularly marked by ECM alterations and the onset of fibrosis. Finally, in Chapter 26, we evaluate the predictive value of mucosal eosinophils and the serum biomarker eotaxin-1, a selective chemoattractant for eosinophils, in relation to response to VEDO induction therapy in patients with IBD. VEDO has the capacity to bind to several types of immune cells, General introduction and outline of the thesis
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