Title of project
Gut Hormones and Metabolic Risk in Bile Acid Diarrhoea: Investigating Diagnostic Biomarkers, Mechanisms of Disease and Translational Treatments
Abstract
Bile acid diarrhoea (BAD) is a common cause of chronic diarrhoea estimated to affect 1% of the population. Patients with the condition frequently have symptoms of severe diarrhoea for several years before diagnosis at it lacks a definitive diagnostic blood test. Principal treatment with bile acid sequestrants is often insufficient to gain full symptom remission. Studies from Gentofte Hospital have highlighted that patients with BAD are at increased risk of metabolic diseases and that translational use of once-daily liraglutide is superior to bile acid sequestrants in managing symptoms of diarrhoea. A recent publication from Institute of Metabolic Science, has highlighted the understudied hormone insulin-like peptide 5 (INSL5) is related to symptoms in BAD. INSL5 was elevated in patients with BAD, with patients with a higher INSL5 level more likely to have a watery stool type. Additionally, the study highlighted INSL5 is raised in a subset of patients with irritable bowel syndrome with diarrhoea and that this sub-group had symptom improvement with anti-sickness medication ondansetron.
This project proposes a partnership between Gentofte Hospital and the Institute of Metabolic Science to build on these discoveries using multiple research modalities including gut hormone measurements, qualitative patient data, magnetic resonance imaging, and treatment interventions. The project will aim to:
- Develop a diagnostic blood test for BAD with gut hormone and metabolic marker measurements
and explore the mechanisms of increased risk of metabolic diseases in BAD - Further explore gut hormone levels in chronic diarrhoea and validate if ondansetron has therapeutic
potential. - Assess if once weekly glucagon-like peptide 1 receptor agonists are an effective treatment to both
manage symptoms and reduce metabolic risk in patients with BAD.
