Constipation-Predominant Irritable Bowel Syndrome Females Have Normal Colonic Barrier and Secretory Function

Am J Gastroenterol. 2017 Jun;112(6):913-923. doi: 10.1038/ajg.2017.48. Epub 2017 Mar 21.

Abstract

Objectives: The objective of this study was to determine whether constipation-predominant irritable bowel syndrome (IBS-C) is associated with changes in intestinal barrier and secretory function.

Methods: A total of 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g 13C mannitol and 1 g lactulose), measurements of duodenal and colonic mucosal barrier (transmucosal resistance (TMR), macromolecular and Escherichia coli Bio-Particle translocation), mucosal secretion (basal and acetylcholine (Ach)-evoked short-circuit current (Isc)), in vivo duodenal mucosal impedance, circulating endotoxins, and colonic tight junction gene expression.

Results: There were no differences in the in vivo measurements of barrier function between IBS-C patients and healthy controls: cumulative excretion of 13C mannitol (0-2 h mean (s.e.m.); IBS-C: 12.1 (0.9) mg vs. healthy: 13.2 (0.8) mg) and lactulose (8-24 h; IBS-C: 0.9 (0.5) mg vs. healthy: 0.5 (0.2) mg); duodenal impedance IBS-C: 729 (65) Ω vs. healthy: 706 (43) Ω; plasma mean endotoxin activity level IBS-C: 0.36 (0.03) vs. healthy: 0.35 (0.02); and in colonic mRNA expression of occludin, zonula occludens (ZO) 1-3, and claudins 1-12 and 14-19. The ex vivo findings were consistent, with no group differences: duodenal TMR (IBS-C: 28.2 (1.9) Ω cm2 vs. healthy: 29.8 (1.9) Ω cm2) and colonic TMR (IBS-C: 19.1 (1.1) Ω cm2 vs. healthy: 17.6 (1.7) Ω cm2); fluorescein isothiocyanate (FITC)-dextran (4 kDa) and E. coli Bio-Particle flux. Colonic basal Isc was similar, but duodenal basal Isc was lower in IBS-C (43.5 (4.5) μA cm-2) vs. healthy (56.9 (4.9) μA cm-2), P=0.05. Ach-evoked ΔIsc was similar.

Conclusions: Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.

MeSH terms

  • Acetylcholine / pharmacology
  • Adult
  • Case-Control Studies
  • Cholinergic Agonists / pharmacology
  • Claudins / genetics
  • Colon / drug effects
  • Colon / pathology
  • Colon / physiopathology*
  • Constipation / etiology
  • Duodenum / drug effects
  • Duodenum / pathology
  • Duodenum / physiopathology*
  • Electric Impedance
  • Endotoxins / blood
  • Female
  • Gene Expression
  • Humans
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology*
  • Irritable Bowel Syndrome / complications
  • Irritable Bowel Syndrome / genetics
  • Irritable Bowel Syndrome / physiopathology*
  • Lactulose / metabolism*
  • Mannitol / metabolism*
  • Middle Aged
  • Occludin / genetics
  • Permeability
  • RNA, Messenger / metabolism*
  • Tight Junctions / genetics
  • Zonula Occludens Proteins / genetics

Substances

  • Cholinergic Agonists
  • Claudins
  • Endotoxins
  • Occludin
  • RNA, Messenger
  • Zonula Occludens Proteins
  • Mannitol
  • Lactulose
  • Acetylcholine