Healthcare (Commonwealth Union) – Researchers from the University of Cambridge have discovered that high concentrations of a hormone present in gut cells may be a key factor behind many cases of chronic diarrhoea and maybe the reason for up to 40% of patients with diarrhoea-predominant irritable bowel syndrome (IBS).
The findings, published in the journal Gut, may pave the way for a blood test and open the door to potential new treatments.
Normally, when food is consumed, the liver releases bile acids to break down fats so they can be absorbed. These bile acids travel into the upper small intestine and are usually reabsorbed further down.
In about one in 100 people, however, this process malfunctions due to a condition called bile acid diarrhoea (also known as bile acid malabsorption). In these cases, the bile acids are not fully reabsorbed and instead reach the large intestine, where they can cause sudden, watery diarrhoea and, in some cases, incontinence.
Diagnosing bile acid diarrhoea is challenging since no standard blood tests currently exist. Many affected individuals are instead diagnosed with IBS, a broad term covering various digestive disorders. It is estimated that around one in 20 people has IBS, and of these, roughly a third who primarily experience diarrhoea may actually have undiagnosed bile acid diarrhoea.
Previous research in mice has indicated that a gut hormone called Insulin-Like Peptide 5 (INSL5) — produced by cells located in the lower colon and rectum — may contribute to chronic diarrhoea. These cells release INSL5 when exposed to irritation from bile acids.
At the University of Cambridge’s Institute of Metabolic Science, scientists have been evaluating whether this hormone might also be associated with chronic diarrhoea in humans.
Earlier, a University of Adelaide study into stimulating the gut hormone GLP-1 — the same hormone targeted by popular weight-loss medications — found that administering a bile acid enema to healthy participants boosted GLP-1 release but unexpectedly caused diarrhoea. When the Cambridge researchers re-examined samples from this trial, they discovered that the bile acid enema also led to a sharp but temporary increase in INSL5 levels. Importantly, the higher the INSL5 concentration, the more urgently participants needed to use the bathroom, strongly suggesting that INSL5 is a key factor in chronic diarrhoea.
Further analysis of samples provided by Professor Julian Walters at Imperial College London, including those from patients suffering from bile acid diarrhoea, reinforced these findings. While INSL5 levels were nearly undetectable in healthy individuals, they were significantly elevated in patients with bile acid diarrhoea. Moreover, higher INSL5 levels correlated with more watery stool samples.
Dr Chris Bannon, the lead author of the study from the University of Cambridge, indicated that
the discovery is particularly exciting because it suggests that this hormone may play a significant role in the symptoms of this often-misunderstood condition. He further indicated that it also opens the possibility of developing a blood test to diagnose bile acid diarrhoea, provided that elevated INSL5 levels are unique to these patients.
“When you go to the doctor with chronic diarrhoea, it’s likely they’ll test for food intolerances, rule out an infection or look for signs of inflammation. There has been significant research interest in the microbiome, but gut hormones have been neglected. But it’s becoming increasingly clear that gut hormones play an important role in things like gut health and weight management.”
INSL5 may also offer a new target for treatment. Dr Bannon and his team received additional samples from Professor Robin Spiller at the University of Nottingham, who had treated IBS patients with ondansetron — an anti-sickness drug that blocks INSL5 activity in mice. When the Cambridge researchers analysed these samples, they found that about 40% of the patients had elevated INSL5 levels despite having tested negative for bile acid malabsorption. Notably, these patients showed the strongest response to ondansetron.
