Functional, temporal and spatial variability of the intestinal microbiome in the pathogenesis of inflammatory bowel disease.

Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders (IBD) characterized by relapsing inflammation of the gut. Surgical resection of the affected intestine is required in 30% of UC and 80% of CD patients. Alterations in the gut microbial composition (called dysbiosis) have shown to play a key role in IBD. To what extent the inflammatory infiltrate influences dysbiosis, is unknown. Dysbiosis might be associated to active inflamed sites as is shown for mucosal microbiota in CD. In UC, inflammation starts in the rectum and spreads proximal to end in a sharp delineation to normal mucosa in the colon. This delineation is not dependent on anatomic barriers and remains an enigma. In this project, we want to gain understanding on the events triggering dysbiosis. We first aim to study spatial variability by characterizing microbial differences in UC at the sharp border between normal and affected tissue. Second, we will investigate if compositional or functional microbial changes are a cause or consequence of inflammation by studying the microbiota during and after resolution of inflammation in different clinical scenarios mimicking the natural onset of disease. Third, we will investigate if dysbiosis in patients can be reversed by fecal bacteriotherapy and if this improves symptoms and lesions. Our project will allow enterotype description, ecosystem shift analysis and potential discovery of new diagnostic, predictive or therapeutic strategies in IBD.