Gut Hormone INSL5 Links Bile Acids to Diarrhea Severity | Research

The takeaway

Rectal bile acids stimulate release of the gut hormone INSL5, and higher INSL5 levels correlate with worse diarrhea in bile acid diarrhea patients.

INSL5 correlated with severity
Higher blood levels of INSL5 linked to worse diarrhea symptoms

What the researchers found

Rectal bile acid exposure stimulates INSL5 secretion in humans, and circulating INSL5 levels are elevated and associated with diarrhea severity in bile acid diarrhea patients.

Why it matters

Identifying INSL5 as a mediator between bile acids and colonic motility could lead to new diagnostic markers and treatment targets for bile acid diarrhea.

How the study worked

Immunoassay-based measurement of INSL5 in serum/plasma samples from previously conducted studies of healthy volunteers and patients with chronic diarrhea.

What this study cannot tell us

Used samples from previously conducted studies rather than a prospective design. The correlation between INSL5 and diarrhea severity does not prove causation.

How to read the evidence

Translational study using a novel immunoassay on archived human samples — provides mechanistic insight but limited by retrospective sample use.

When this study was published

Published in 2026; introduces a new assay for INSL5 measurement.

The bigger picture

This connects the enteroendocrine system to functional bowel disorders, suggesting that peptide hormones from the distal gut play underappreciated roles in GI symptoms.

Questions still open

Could blocking INSL5 signaling reduce bile acid diarrhea symptoms?
Is INSL5 a useful clinical biomarker for diagnosing bile acid diarrhea?

Common questions

What is INSL5?

INSL5 (insulin-like peptide 5) is a hormone produced by specialized cells in the lower colon that appears to promote colonic motility and may contribute to diarrhea when overproduced.

What is bile acid diarrhea?

Bile acid diarrhea occurs when excess bile acids reach the colon and stimulate water secretion and motility, causing frequent loose stools. It affects an estimated 1 in 100 people.

Read the original research

Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea.

Gut, 75(2), 278-288

View on PubMed ↗Publisher’s paper ↗

Citation

Bannon, Christopher A; Walters, Julian R F; Wu, Tongzhi; Kay, Richard G; Punnoose, Austin; Spiller, Robin C; Wilson, Jonathan; Verdino, Petra; Barker, Peter; Burling, Keith; Horowitz, Michael; Rayner, Christopher K; Ford, Alexander C; Reimann, Frank; Gribble, Fiona M. (2026). Insulin-like peptide 5 is released in response to bile acid in the rectum and is associated with diarrhoea severity in patients with bile acid diarrhoea.. Gut, 75(2), 278-288. https://doi.org/10.1136/gutjnl-2025-335393