New Insights into Gut Hormone's Role in Chronic Diarrhea Could Lead to Innovative Diagnostics and Therapies

Recent research conducted by scientists at the University of Cambridge has uncovered a significant connection between a hormone produced in the gut and chronic diarrhea, offering promising avenues for better diagnosis and treatment. Elevated levels of the hormone insulin-like peptide 5 (INSL5), which is generated by cells at the end of the colon and rectum, appear to be linked to persistent diarrhea conditions. This discovery could explain up to 40% of cases involving irritable bowel syndrome with diarrhea (IBS-D), a common but poorly understood disorder.

The study, published in the journal Gut, highlights how bile acids—substances released during fat digestion by the liver—play a role in gut irritation when their reabsorption is disrupted. Normally, bile acids are absorbed in the small intestine and recycled, but in some individuals, they escape this process, entering the colon and causing symptoms like urgent, watery diarrhea. Such bile acid diarrhea (BAD) remains challenging to diagnose since there are no routine blood tests, and many cases are misclassified as IBS.

Previous animal studies indicated that INSL5 might be involved in diarrhea caused by bile acids. Using a novel antibody test developed in collaboration with pharmaceutical company Eli Lilly, researchers measured tiny amounts of INSL5 in human samples. They observed that after administering a bile acid enema to healthy volunteers, INSL5 levels spiked temporarily, correlating with increased urgency and bowel movements.

Further analysis involving patients with bile acid diarrhea revealed that INSL5 levels were significantly higher compared to healthy individuals, with higher levels correlating with more watery stool samples. These findings suggest that INSL5 could serve as a biomarker for diagnosing bile acid diarrhea. Dr. Chris Bannon, the lead researcher, emphasized the potential of this discovery to transform diagnosis and treatment strategies.

Current treatments for bile acid diarrhea include medications known as bile acid sequestrants, but these work effectively in only around 66% of cases. The study also explored the therapeutic potential of ondansetron, a drug that blocks INSL5 action and is normally used for nausea. Patients with increased INSL5 levels responded best to ondansetron, indicating that targeting this hormone might offer new treatment options.

The research underscores the importance of gut hormones in gastrointestinal health, a field gaining attention for its potential to improve patient outcomes. Dr. Bannon explained that INSL5 functions as a toxin detector, identifying harmful substances like excess bile acids in the colon and helping the body eliminate them. However, chronic activation of this pathway can cause severe symptoms, as seen in BAD.

This groundbreaking work opens pathways for improved diagnostic tests and personalized treatments for chronic diarrhea conditions, potentially reducing misdiagnoses and enabling more effective management. Future studies aim to better understand how drugs like ondansetron can be repurposed or enhanced to help patients suffering from this often misunderstood condition.

source: https://medicalxpress.com/news/2025-07-discovery-role-gut-hormone-chronic.html