Lipidomic, microbial and functional characterization of triggers of post-operative recurrence in Crohn’s disease

Crohn’s disease (CD) is a chronic, relapsing inflammatory bowel disease (IBD) which is caused by a complex interaction of genetic, immune, microbial and environmental factors. Surgical resection is needed in up to 70% of CD patients. At the luminal side of the intestine, pioneering work of our group demonstrated that in two-thirds of patients undergoing surgery, new CD lesions recur within weeks to months, but only in the presence of the fecal stream. At the external side of the intestine, a pathognomic phenomenon of CD is observed, ie.“creeping fat”, which is a local hyperplasia of mesenteric adipose tissue migrating to the sites of intestinal inflammation. However, which luminal components are triggering post-operative recurrence and whether creeping fat has a pathological or protective role in CD, is still not clear. 

The current project aims to identify triggers of post-operative recurrent CD, by focusing both on the external and the luminal side of the intestine. First, we will profile the lipidomic landscape of creeping and paired mesenteric fat at the time of surgery, and assess if these lipid signatures are predictive for post-operative recurrence. Next, we will characterize fecal components predicting recurrence by combining shotgun metagenomics with metabolomics. Furthermore, to get a better functional understanding, these fecal contents will also be exposed to matched ileal epithelial cells using in vitro 2D transwells derived from organoids.