Journal Article

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

Dalenberg, Daniel A, MacNaughton, Wallace K, Moses, Natalie, Katzka, David A, Dyer, Roy B, Linden, David R, Peters, Stephanie A, Singh, Ravinder J, Grover, Madhusudan, Turner, Jerrold R, Weber, Christopher, Smyrk, Thomas C, Camilleri, Michael, Edogawa, Shoko, Sundt, Wendy J, Farrugia, Gianrico, Mazzone, Amelia

2017

Overview

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. A total of 19 IBS-C patients and 18 healthy volunteers (all females) underwent saccharide excretion assay (0.1 g C 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. There were no differences in the in vivo measurements of barrier function between IBS-C patients and healthy controls: cumulative excretion of C 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 cm vs. healthy: 29.8 (1.9) Ω cm ) and colonic TMR (IBS-C: 19.1 (1.1) Ω cm vs. healthy: 17.6 (1.7) Ω cm ); 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 ) vs. healthy (56.9 (4.9) μA cm ), P=0.05. Ach-evoked ΔIsc was similar. Females with IBS-C have normal colonic barrier and secretory function. Basal duodenal secretion is decreased in IBS-C.

• Publisher: Wolters Kluwer Health Medical Research, Lippincott Williams & Wilkins
• Subject: 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 / Escherichia coli / Female / Gastroenterology / 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