Guanylin

Where it comes from

Made in

Goblet and epithelial cells of the colon, secreted into the gut lumen

Sent out by

Salt intake and distension; it acts from the lumen side

Acts on

• Intestinal epithelium (chloride and bicarbonate secretion)
• Gut pain nerves (indirectly, through cGMP)

What it does

• Drives fluid into the gut and so softens stool ¹
• Lowers gut pain signalling through cGMP
• Its loss is linked with the growth of colon cancer ¹

In medicine

• Linaclotide (2012) and plecanatide (2017) are GC-C agonists approved for chronic constipation and IBS with constipation ²
• Traveller’s diarrhoea from E. coli heat-stable toxin is the same receptor overdriven ¹

Beyond the body’s own use

• Two 12-week randomised trials settled the dose linaclotide was approved on: about a fifth of patients reached the primary endpoint against 3% to 6% on placebo ³
• GC-C agonists are studied for the prevention of colorectal cancer, on the finding that guanylin is lost early in the disease. Dolcanatide reached the colon and raised cGMP there in a phase 1 trial in healthy volunteers, which is as far as that line has got ⁴
• Guanylin itself is not given. The medicines are stabilised copies that survive the gut and act from inside it, so almost none of the dose is absorbed, which is also why their side effects are confined to the bowel ²