Scientists have uncovered the hormonal cause of irritable bowel syndrome

Unexplained bouts of diarrhea in millions of people may be associated with the hormone INSL5, which is dramatically activated when bile acids enter the colon. This is stated in the material of the Science Daily magazine, which Izvestia reviewed on July 30.

According to the article, elevated INSL5 levels can explain up to 40% of cases of the diarrheal variant of irritable bowel syndrome, IBS-D. This condition is often misdiagnosed, while the real cause may be impaired absorption of bile acids.

As scientists explain, in healthy people, bile acids secreted by the liver to digest fats return to the bloodstream in the lower small intestine. However, when this mechanism is disrupted, the acids reach the colon and irritate it, causing a violent reaction, including the activation of the hormone INSL5, which in turn triggers diarrhea.

Earlier studies in mice had already pointed to the role of INSL5, but the lack of methods prevented us from confirming this in humans. The new development has made it possible to accurately measure the concentration of the hormone in the blood. Using these technologies, the Cambridge team identified a direct link between the level of INSL5 and the severity of symptoms, both in volunteers and in patients with an established diagnosis.

The analysis of data obtained during the experiment with bile acid-based enemas was particularly revealing: participants who had sharply increased INSL5 after the procedure also experienced more acute diarrhea. This confirmed the key role of the hormone in the pathogenesis of the disease.

The authors also tested the effect of the drug ondansetron, known as an INSL5 blocker in mice. 40% of patients with IBS-D who were given this remedy had a positive response to treatment, despite the fact that they had no confirmed bile malabsorption. This opens up the prospect for its use in therapy.

"When you go to a doctor with chronic diarrhea, they will most likely perform a food intolerance test, rule out infection, or look for signs of inflammation. The microbiome is interesting for researchers, but intestinal hormones are still ignored. However, it is becoming increasingly clear that gut hormones play an important role in aspects such as intestinal health and weight control," said Dr. Christopher Bannon.

The researchers also raise an important physiological question — why does the body need a hormone that causes diarrhea. According to Bannon, INSL5 is a kind of "danger signal" that is activated when potentially toxic substances enter the intestine. However, constant stimulation leads to disruption of the normal functioning of the gastrointestinal tract and severe symptoms.

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