An activating gucy2c mutation causes impaired contractility and fluid stagnation in the small bowel

Scand J Gastroenterol. 2016 Nov;51(11):1308-15. doi: 10.1080/00365521.2016.1200139. Epub 2016 Jun 24.

Abstract

Objective: Familial GUCY2C diarrhoea syndrome (FGDS) is caused by an activating mutation in the GUCY2C gene encoding the receptor guanylate cyclase C in enterocytes. Activation leads to increased secretion of fluid into the intestinal lumen. Twenty percent of the patients have increased risk of Crohn's disease and intestinal obstruction (CD, 20%) and the condition resembles irritable bowel syndrome with diarrhoea. We aimed to describe fluid content, contractility, peristaltic activity and bowel wall thickness in the intestine in fasting FGDS patients, using ultrasound, with healthy volunteers serving as controls.

Methods: Twenty-three patients with FGDS and 22 healthy controls (HC) were examined with a Logiq E9 scanner in a fasting state. Bowel wall thickness was measured and fluid-filled small bowel loops were counted using three-dimensional (3D) magnetic positioning navigation. The HC ingested 500 ml PEG solution, an electrolyte balanced, non-absorbable solution, in order to investigate the contractions of the small bowel.

Results: The fasting 23 FGDS patients had significantly higher number of fluid-filled small bowel segments compared to 22 fasting HC, p < 0.001. A high number of non-occlusive contractions in the ileum was observed, which was significant when compared to HC after ingesting PEG solution, p < 0.016. An increase in intestinal wall thickness or other signs of CD were not observed.

Conclusions: FGDS is characterised by multiple, fluid-filled small bowel loops with incomplete contractions and fluid stagnation in fasting state. These findings may play a role in the increased risk of bowel obstruction as well as IBS-like symptoms observed in these patients.

Keywords: Crohńs disease; GUCY2C; dysmotility; familial GUCY2C diarrhoea syndrome; guanylate cyclase C; ultrasonography.

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • Crohn Disease / diagnostic imaging
  • Diarrhea / etiology
  • Diarrhea / physiopathology*
  • Female
  • Humans
  • Ileum / diagnostic imaging
  • Ileum / physiopathology*
  • Intestinal Diseases / diagnostic imaging
  • Intestinal Diseases / genetics*
  • Intestinal Obstruction / diagnostic imaging
  • Intestine, Small / diagnostic imaging
  • Intestine, Small / physiopathology*
  • Linear Models
  • Male
  • Middle Aged
  • Mutation
  • Peristalsis*
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled / genetics*
  • Receptors, Peptide / genetics*
  • Ultrasonography
  • Young Adult

Substances

  • Receptors, Peptide
  • GUCY2C protein, human
  • Receptors, Enterotoxin
  • Receptors, Guanylate Cyclase-Coupled