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

Abstract

Objective To determine if constipation predominant IBS (IBS-C) is associated with changes in intestinal barrier and secretory function. Design 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 E. coli Bio-Particle translocation), mucosal secretion (basal and 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 and healthy: cumulative excretion of 13C mannitol (0–2 hr mean (SEM); IBS-C: 12.1 (0.9) mg vs healthy: 13.2 (0.8) mg) and lactulose (8–24 hr; 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, ZO 1–3, and claudins 1–12, 14–19. 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); FITC Dextran (4 kDa) and E. coli Bio- Particle flux. Colonic basal Isc was similar, however, duodenal basal Isc was lower in IBS-C (43.5 (4.5) µA*cm2) vs healthy (56.9 (4.9) µA*cm2), 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.

Vasoactive Intestinal Polypeptide and Mast Cells Regulate Increased Passage of Colonic Bacteria in Patients With Irritable Bowel Syndrome

“…Previous studies on I sc and IBS are mostly lacking, however, recently Peters et al 54 showed a similar I sc in IBS-C and HCs, which is in line with our findings and indicates an increased bacterial uptake in IBS, even in circumstances where ion transport is unchanged. To further determine changes in permeability due to tight junction components, we chose to study occludin and ZO-1 expression, as main constituents of the apical junctions, based on previous reports demonstrating its deregulation in the colon of IBS 13 Our study confirms previous data and extends its contribution to bacteria-mediated epithelial alterations.…”

Leaky gut: mechanisms, measurement and clinical implications in humans

“…Two techniques are available: first, confocal endomicroscopy, which shows leaks of intravenously administered fluorescein into the gut lumen during endoscopy49 (eg, in response to food-associated changes in the intestinal mucosa of patients with diarrhoea-predominant IBS); and second, endoscopic mucosal impedance, in which a 2 mm diameter catheter is passed through an endoscope and placed in contact with the duodenal mucosa under direct visualisation, and two circumferential sensors, placed 2 mm apart on the mucosa for 0.10 s, in the four quadrants of the duodenum with a decompressed lumen, and all fluid aspirated 50. The studies of food-associated changes during these challenge tests provide some evidence that there can be barrier changes that may indeed support the concept of transient ‘leakiness’ of the gut.…”

The Gut Microbiome in Adult and Pediatric Functional Gastrointestinal Disorders

“…Changes in small intestinal 93 and colonic secretion represents another pathophysiologic disturbance in FGIDs that may be influenced by the gut microbiome 48 ( Figure 3 ). Secretory mechanisms are common therapeutic targets 94, 95 of medications used to treat FGIDs.…”