Towards novel biomarkers and rational nutritional interventions in Inflammatory Bowel Disease

To improve the well-being of patients with Inflammatory Bowel Disease (IBD), more insight is needed on the effects of dietary interventions on disease outcome. An stressful invasive endoscopy is needed to assess disease activity and this could be avoided if non-invasive biomarkers could determine the disease activity. In this thesis, we aimed to investigate the role of gut-microbe interactions in vitro and the modulating effects of nutritional riboflavin supplementation on the human gut microbiome composition, while simultaneously evaluating novel biomarkers (biomarkers of inflammation, intestinal permeability and systemic oxidative stress) for monitoring of disease activity. First, we give an overview of different in vitro co-culture models for studying host-microbe interactions and demonstrated mutualistic interactions between the intestinal epithelium and beneficial, commensal Faecalibacterium prausnitzii bacteria. Furthermore, we performed a prospective clinical intervention study with riboflavin (RISE-UP Study) in Crohn’s disease, and showed an improvement on symptoms, reduced systemic inflammation and oxidative stress, but interestingly, no clear effects on the gut microbiota. In addition, we demonstrated that (combinations of) inflammatory biomarkers correlate well with gut inflammation (fecal calprotectin and endoscopy). Additionally, we found that oral 52Cr-EDTA could assess gut permeability and plasma free thiols can be used as novel biomarker for systemic oxidative stress in relation to gut inflammation. The findings presented in this thesis contribute to the development of novel biomarkers for IBD disease activity and to better understanding of the potential of dietary modulation of inflammation and host-microbe interactions as therapeutic strategy to improve disease outcome in patients with IBD.