When we eat the liver releases bile acid to help break down fats for absorption. This bile acid enters the upper part of the small intestine and is normally reabsorbed in the lower part.

Diagnosing bile acid diarrhoea is challenging as there are currently no standard blood tests for it. Many patients are misdiagnosed with irritable bowel syndrome a broad category covering various digestive issues. It's estimated that around 1 in 20 people have IBS and among those whose main symptom is diarrhoea up to one-third may actually have undiagnosed bile acid diarrhoea.

Researchers at the Institute of Metabolic Science University of Cambridge have been investigating whether the hormone INSL5 plays a role in chronic diarrhoea. This has been made possible through a collaboration with pharmaceutical company Eli Lilly which developed a highly sensitive antibody test capable of detecting tiny amounts of INSL5.

A previous study conducted at the University of Adelaide aimed to stimulate the release of GLP-1 a hormone central to weight-loss drugs by administering a bile acid enema to healthy volunteers. While GLP-1 levels increased as expected the team also observed a spike in INSL5 levels which was linked to urgent bowel movements. This suggested that INSL5 might be a key factor contributing to diarrhoea.

The Cambridge researchers then analysed samples provided by Professor Julian Walters at Imperial College London which included data from patients with bile acid diarrhoea. They discovered that INSL5 levels were significantly higher in these patients compared to healthy controls. Moreover elevated INSL5 levels were associated with more watery stool samples strengthening the evidence that this hormone plays a central role in chronic diarrhoea.

Dr. Chris Bannon lead author from the University of Cambridge highlighted that elevated INSL5 levels could be key to diagnosing bile acid diarrhoea a condition often misunderstood and misdiagnosed. He noted that while gut microbiome research has grown gut hormones like INSL5 have been largely overlooked.

The team also analyzed samples from IBS patients treated with ondansetron a drug known to block INSL5 in mice. They found that about 40% had raised INSL5 levels and responded best to the treatment even without bile acid malabsorption.

Though the exact mechanism remains unclear ondansetron’s side effect of constipation suggests it may counteract INSL5’s diarrhoeal effects. Current treatments like bile acid sequestrants help only two-thirds of patients. Dr. Bannon speculates that INSL5 may act as a poison sensor prompting diarrhoea when bile acids irritate the colon but when overactive it causes debilitating symptoms.

Source: https://www.cam.ac.uk/research/news/discovery-of-role-of-gut-hormone-in-chronic-diarrhoea-could-aid-development-of-new-tests-and