Scientists from the University of Cambridge have discovered that high levels of a hormone found in the gut, called INSL5, may be the cause behind many cases of chronic diarrhea.
Their research suggests this hormone may be responsible for up to 40% of cases of diarrhea in people diagnosed with irritable bowel syndrome (IBS).
The findings, published in the journal Gut, could lead to new tests and treatments for people who suffer from ongoing digestive problems.
Normally, the liver produces bile acid after we eat to help break down fats. Bile acid travels to the small intestine and should be reabsorbed before it reaches the large intestine. But in some people, this doesn’t happen properly.
Instead, bile acid moves into the colon, where it causes watery and urgent diarrhea. This condition is called bile acid diarrhea or bile acid malabsorption and affects about 1 in every 100 people.
Bile acid diarrhea can be hard to diagnose. Many people with this problem are told they have IBS, a general term used for several digestive conditions. Experts believe that one in three IBS patients who mainly have diarrhea may actually have undiagnosed bile acid diarrhea.
To explore this, researchers studied a hormone called Insulin-Like Peptide 5 (INSL5), which is made by cells in the lower part of the gut. INSL5 is released when these cells are irritated by bile acids. In mice, this hormone has been linked to diarrhea, but this is one of the first studies to confirm the same in humans.
The Cambridge team used a new antibody test developed by Eli Lilly to measure small amounts of INSL5 in blood samples. They reviewed samples from a study where healthy volunteers were given bile acid enemas.
The enemas caused temporary diarrhea and a spike in INSL5 levels. The higher the INSL5, the faster people had to use the toilet, showing a direct link between the hormone and diarrhea symptoms.
Next, the researchers looked at samples from people with bile acid diarrhea and compared them to healthy individuals. They found that INSL5 levels were almost undetectable in healthy people, but very high in patients with bile acid diarrhea. Not only that, but higher hormone levels were linked to more watery stool.
Dr. Chris Bannon, the lead author, said the discovery was exciting because it could lead to a blood test that helps doctors identify this specific kind of diarrhea. Right now, many people are misdiagnosed, and gut hormones like INSL5 are not routinely checked.
The study also points to a possible treatment. Researchers looked at patients with IBS who had not been diagnosed with bile acid problems but still had high INSL5 levels.
These patients responded well to a drug called ondansetron, which is normally used to prevent nausea. In mice, this drug is known to block INSL5. The team now believes this medication, or a new version of it, could help many people with chronic diarrhea.
Dr. Bannon explained that INSL5 might act like a natural alarm system for the body. Bile acids aren’t supposed to reach the colon—they can irritate the gut and harm good bacteria. So, INSL5 might help flush them out quickly. But when this system is triggered all the time, it can cause serious problems.
This research, supported by the Medical Research Council, Wellcome, and the National Institute for Health and Care Research, offers hope for people who have been struggling with unexplained digestive issues. By better understanding how INSL5 works, scientists may soon develop better tests and treatments that target the real cause of symptoms.
If you care about gut health, please read studies about how junk food harms your gut health, and how probiotics can protect gut health.
For more information about health, please see recent studies about how fiber affects weight loss and your overall health, and results showing why a glass of red wine is good for your gut.
The study is published in Gut.
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