Towards Personalised Therapies for Crohn’s Disease Using Primary Intestinal Enteroids (360G-Wellcome-204267_Z_16_Z)

In the UK an estimated 620,000 people suffer from inflammatory bowel disease (IBD). Poor access to primary tissue and a lack of animal models that faithfully reproduce the human condition has left us with an inadequate understanding of how to diagnose and treat IBD. These issues are exemplified by Crohn’s disease (CD), a debilitating disease where chronic inflammation leads to intestinal perforation that requires surgical removal. Here we propose to apply our recently published intestinal culture platform to model CD to address 2 interlinked objectives: 1) Generate an in-vitro intestinal enteroid model of Crohn’s disease. There are currently no reliable in-vitro models of CD. To create a new model of CD we will generate "mini-intestines" using intestinal biopsy from patients with CD. 2) Create a platform to study microbiota dysbiosis. Changes in the types of bacteria in the intestine is believed to be important in the initiation and progression of CD, however this has not been well studied. Here we will validate a bacterial injection platform into CD enteroids that can be used for future studies on microbiota dysbiosis.