Gut Hormone INSL5 Links Bile Acids to Diarrhea Severity

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

Bannon, Christopher A et al.·Gut·2026·
RPEP-148372026RETHINKTHC RESEARCH DATABASErethinkthc.com/research

Quick Facts

Study Type
Not classified
Evidence
Not graded
Sample
Not reported

What This Study 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.

Key Numbers

How They Did This

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

Why This Research 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.

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.

What This Study Doesn't Tell Us

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

Questions This Raises

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

Trust & Context

Key Stat:
INSL5 correlated with severity Higher blood levels of INSL5 linked to worse diarrhea symptoms
Evidence Grade:
Translational study using a novel immunoassay on archived human samples — provides mechanistic insight but limited by retrospective sample use.
Study Age:
Published in 2026; introduces a new assay for INSL5 measurement.
Original Title:
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.
Published In:
Gut, 75(2), 278-288 (2026)
Database ID:
RPEP-14837

Evidence Hierarchy

Meta-Analysis / Systematic Review
Randomized Controlled Trial
Cohort / Case-Control
Cross-Sectional / ObservationalSnapshot without intervening
This study
Case Report / Animal Study
What do these levels mean? →

Frequently Asked 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 More on RethinkPeptides

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Cite This Study

RPEP-14837·https://rethinkpeptides.com/research/RPEP-14837

APA

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

MLA

Bannon, Christopher A, et al. "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, 2026. https://doi.org/10.1136/gutjnl-2025-335393

RethinkPeptides

RethinkPeptides Research Database. "Insulin-like peptide 5 is released in response to bile acid ..." RPEP-14837. Retrieved from https://rethinkpeptides.com/research/bannon-2026-insulinlike-peptide-5-is

Access the Original Study

Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.

This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.