Research Findings –  Gut Hormone in Human Health and Disease (GutHHD)

 How Gut Hormones may cause Chronic Diarrhoea explained

Motilin profileMeasuring multiple gut hormones simultaneously including motilin using mass spectrometry in healthy volunteers

In this study we recruited 10 healthy volunteers with no history of an endocrine or gastrointestinal condition, to undergo a day visit, to have a full 4 hour fasting gut hormone profile, and 2 hours post meal profile.

Motilin is an unusual hormone – most gut hormones are low whilst we fast, and rise when food enters the gut.  Motilin however fluctuates whilst we fast. 

Therefore in order to study Motilin, our study design is set up to have adequate fasting samples to capture how motilin levels go up and down.

Motilin acts to increase gut movements (making it a very well named hormone (!)) in between meals. 

Using mass spectrometry motilin was measured alongside other gut hormones including GIP and CCK, and the pancreatic hormones insulin and glucagon.

Exploring gut hormone levels in patients with bile acid diarrhoea

Bile acid diarrhoea is a common but underdiagnosed condition.  It is estimated to affect 1% of the population, and up to 1/3 of patients with irritable bowel syndrome who experience diarrhoea as their main symptom.

Patients with bile acid diarrhoea experience urgency, loose stools and frequent unpredictable bowel motions.

There is currently not a definitive blood test to diagnose the condition, and the main treatment is with bile acid binders called bile acid sequestrants.

Bile Acid DiarrhoeaSymptoms result from bile acids entering the colon.  Usually, bile acids are absorbed before the colon, triggering release of a hormone called FGF19 to prevent further bile acid production.

Bile acids are known to be a potent trigger for release of several gut hormones – including gut hormones which increase gut movements.

Our studies in particular focus on a colon hormone called Insulin-like peptide 5 (INSL5), which increases colonic movements and can be triggered by bile acids.

Two meal studyWe have previously recruited 16 volunteers with bile acid diarrhoea to undergo a meal gut hormone profile, with and without their standard bile acid sequestrant treatment.

Additionally some volunteers provided a recorded in-depth interview regarding their symptoms.

We are currently analysing these samples to assess gut hormone levels including INSL5 in patients with bile acid diarrhoea; how sequestrants affect these hormone levels and how these hormone levels relate to gut symptoms and bowel habit.

Presentations of our findings

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry poster

USA Digestive Disesases Week – May 2024

Frontiers in Endocrinology journal – March 2024

Danish Diabetes and Endocrine Academy Endocrinology Symposium on Translating Biomarkers into Clinical Endocrinology – May 2023

Raised insulin-like peptide 5 (INSL5) levels in patients with bile acid diarrhoea and subset of patients with irritable bowel syndrome and relationship with symptoms and bile acid metabolism

USA conference Digestive Diseases Week- May 2024

Determinants of plasma insulin-like 5 levels in humans and effect of rectal bile acid exposure 

USA conference Digestive Diseases Week- May 2023