Study into the aetiology of Inflammatory Bowel Disease
Research type
Research Study
Full title
Study into the aetiology of diseases of the gastrointestinal tract: Investigation into the role of genetic variants, microbiome and immune response in gastrointestinal inflammation
IRAS ID
265959
Contact name
Andrew Smith
Contact email
Sponsor organisation
University College London
Clinicaltrials.gov Identifier
Z6364106/2020/10/14, UCL Data Protection Number
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Inflammatory bowel disease (IBD) is a lifelong condition which can cause debilitating symptoms and be very challenging to manage. The bowel lining has bacteria and toxins which must be contained whilst nutrients and water are absorbed. In IBD, problems with bowel cells’ response to bacteria and an imbalance between helpful and harmful inflammation is connected to the early stages of disease. We know certain patients with IBD have specific mutations (variants) in key immune genes related to how cells handle the clearance of bacterial infection in a process called autophagy. In addition, we also know that the environment can play a role in the development of IBD. The environment has a profound influence on the microbes (bacteria and fungi) that colonise our gastrointestinal tract and changes in microbial composition has also been linked to the development of IBD. How the genetic variants, the environment and the different microbes can result in the development of uncontrolled bowel inflammation still remains unclear.
This study aims to use biopsy and blood samples taken from people with IBD to build a 3D laboratory model, or organoid, of the bowel. We will build organoids that consist of cells that contain specific genetic variants in order to gain an understanding of how these mutations influence the immune response during bacterial infection. This is important as organoids better reflect what is happening in the human body and they can then be tested under different conditions, such as when certain genes related to autophagy are turned on or off, or when cells are exposed to different bacteria. These bacteria can be those commonly known to cause inflammation or based upon those detected in stool or bowel fluid samples from our patients. This approach has the potential to unravel some of the current mysteries surrounding the development of IBD and why only some people respond to current treatments. We may also be able to investigate new therapies safely under laboratory conditions in order to gain some mechanistic insight into how they function in the bowel.
REC name
South West - Frenchay Research Ethics Committee
REC reference
21/SW/0060
Date of REC Opinion
28 Jun 2021
REC opinion
Further Information Favourable Opinion