Gut mucosal gene expression in inflammatory bowel disease:the heterogeneous nature of inflammation

This thesis entitled “Gut mucosal gene expression in inflammatory bowel disease - the heterogeneous nature of inflammation” describes the molecular basis of inflammatory bowel disease (IBD), which has a prevalence of 8:1000 in the Netherlands. IBD is marked by episodes of intestinal inflammation, and may manifest in other organs. Despite a large variety of treatment options, a substantial part of patients remains difficult to treat, and has to try out various (expensive) medications hoping to find one that works. This is a clinical and societal problem, requiring a solution.Within this thesis, the cause of IBD is sought and new opportunities for medical therapy are explored. One of the projects reveals 190 unique DNA variants that affect gut mucosal gene expression, depending of inflammation status. These findings support the theory that a patient-specific genetic background of IBD exists. Using a new technique, ‘single cell sequencing’, gut mucosal cells of IBD patients are investigated. There, it was found that specific cell types are expressing risk genes for IBD. These cells could be specifically targeted using currently available medication. Lastly, the gut mucosal cells of IBD patients are compared with a specific subgroup of IBD patients that has concomitant primary sclerosing cholangitis, a bile duct inflammation disease. Functional differences in inflammatory cells are found that may indicate differences in pathogenesis for this subgroup of the disease.In conclusion, this thesis describes molecular differences between patients with IBD, which may be key to personalized treatment of the disease