Molecular profiling of early events in the pathogenesis of inflammatory bowel disease

Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut and comprises two major forms: Crohn’s disease (CD) and ulcerative colitis (UC). A genetic predisposition is a risk factor for developing IBD, with a peak incidence in early adult life, and ranging beyond the sixth decade of life. It has been shown that the phenotypes of late-onset IBD differ from those in the younger population. Anti-tumor necrosis factor (TNF) therapies have dramatically improved IBD treatment, however, a subset of patients shows no or limited response to this therapy. This clearly illustrates the need for novel therapeutic options. Also, a more intensive treatment early in the course of the disease has already suggested better outcomes. The objective of this study is to unravel the early events in IBD pathogenesis to find new targets for treatment and to identify molecular markers for early diagnosis. The best models to do this are newly diagnosed CD and UC patients, and CD patients with post-operative recurrence. In addition, we will compare early- and late-onset CD and UC.  We will use multiple sources of biological evidence including known genetic variants associated with IBD, mucosal mRNA expression, and mucosal and exosomal miRNA expression. The exploration of exosomes in this context is tantalizing as they are readily available from body fluids by non-invasive means.