Reduced intestinal motility in inflammatory Crohn's Disease optimisation studies on healthy volunteers (MIC 1)

10th August 2015

Status: Ended

Specialism: Lower GI.

Team: Dr Gordon Moran.

Crohn’s disease (CD) is an inflammatory disorder of the gut that may present with symptoms of bloating, nausea and vomiting. Enteroendocrine cells (EEC) constitute 1% of the cells lining the intestinal mucosa. They play a pivotal role in orchestrating gastrointestinal tract (GI) physiology by secreting multiple hormones that control GI functions. EEC hormones, Cholecystokinin, Glucagon-like peptide-1 and Polypeptide YY delay gastric emptying and small bowel transit. Recent data shows that in CD there is a significant increase in EEC expression, while technological advances now allow us to measure GI motility by using functional magnetic resonance imaging techniques.

We hypothesize that a) CD-related symptoms of abdominal bloating, nausea and loss of appetite are caused by altered GI motility b) these changes are associated with an increase in EEC expression c) the altered transit can be mechanistically inhibited through EEC peptide inhibition.

This experimental work is very novel and has a clinical translational potential as it will undoubtedly improve CD-related symptoms. Optimisation experiments in healthy volunteers are now needed before embarking on proof-of-principle pilot work in a CD cohort. We will initially study a cohort of 15 healthy volunteers with the overall aim to investigate the effect of intestinal inflammation on gut motility. We will be investigating this by using functional MRI techniques