Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes

Simon P. Dunlop, M.D.; John Hebden, M.D.; Eugene Campbell, M.B.; Jorgen Naesdal, M.D.; Lars Olbe, M.D.; Alan C. Perkins, Ph.D.; Robin C. Spiller, M.D.


Am J Gastroenterol. 2006;101(6):1288-1294. 

In This Article

Abstract and Introduction

Objectives: Irritable bowel syndrome (IBS) is a heterogeneous condition and defined according to symptoms. Low-grade inflammation has been associated with IBS, particularly that following infection, but whether altered intestinal permeability profiles relate to irritable bowel subtype or onset is uncertain. Our aim was to compare small and large intestinal permeability in various subtypes of IBS to healthy controls.
Methods: Intestinal permeability was measured using 1.8 MBq of 51Cr-EDTA and collecting urine over 24 h; Study 1: patients with diarrhea-predominant postinfectious IBS (N = 15), constipation-predominant IBS (N = 15), and healthy controls (N = 15); Study 2: two groups of diarrhea-predominant IBS (D-IBS), one with a history of onset after acute gastroenteritis (postinfectious) (N = 15) and the other without such a history (nonpostinfectious) (N = 15) both compared with healthy controls (N = 12).
Results: Permeability expressed as percentage of total dose excreted in urine (median [inter-quartile range]). Study 1: Proximal small intestinal permeability was increased in postinfectious IBS (0.19 [0.12-0.23]) in contrast to constipated IBS (0.085 [0.043-0.13]) and controls (0.07 [0.035-0.19]) (p = 0.02). IBS patients with eczema, asthma, or hay fever had increased proximal small intestinal permeability compared with IBS patients without atopy (p = 0.02). Study 2: Small intestinal permeability was greater in nonpostinfectious diarrhea-predominant IBS (0.84 [0.69-1.49]) compared with postinfectious IBS (0.43 [0.29-0.63], p = 0.028) or controls (0.27 [0.2-0.39]), p = 0.001).
Conclusions: Small intestinal permeability is frequently abnormal in diarrhea-predominant IBS. Those without a history of infectious onset appear to have a more severe defect.

Irritable bowel syndrome (IBS) is common, yet the mechanisms by which symptoms arise are poorly understood. IBS is associated with psychological disturbance,[1] food intolerance,[2,3] and prior gastroenteritis.[4] Although normal by conventional criteria, colonic biopsies from patients with IBS demonstrate evidence of increased numbers of chronic inflammatory cells[5,6,7,8,9] and of immune activation.[10] This suggests that at least in some IBS patients, low-grade inflammation may be an important mechanism by which symptoms are generated.[11] We have recently shown that postinfectious irritable bowel syndrome (PI-IBS) is associated with increased numbers of mucosal 5-hydroxytryptamine-containing enterochromaffin (EC) cells, increased mucosal lymphocytes, and less psychiatric illness than irritable bowel patients without an infectious onset.[12] While inflammatory conditions such as acute gastroenteritis,[13,14] celiac disease,[15] and Crohn's disease[16] increase gut permeability, whether particular subtypes of IBS are also associated with altered gut permeability is not well established. Previous studies of gut permeability in IBS by other authors have either assessed only the small bowel with dual sugar probes,[17,18] or used poorly defined groups[19,20,21] prior to consensus classification.[22,23] Our preliminary study[9] using the lactulose/mannitol urinary excretion ratio showed increased small bowel permeability in PI-IBS (who mostly had diarrhea-predominant IBS [D-IBS]) but did not assess colonic permeability. Furthermore, we could not determine the specificity of this finding because we did not study IBS patients either with diarrhea not because of prior infection or without diarrhea. Our underlying hypothesis was that the increased permeability was because of low-grade inflammation, which we have reported in mucosal biopsies in both PI-IBS and D-IBS but not constipation-predominant IBS (C-IBS).[24] We, therefore, undertook two separate studies with different cohorts of patients and healthy controls. The aim of Study 1 was to compare proximal and distal small bowel and large bowel permeability in PI-IBS to healthy controls and C-IBS patients. In Study 2 we determined whether the increased permeability in PI-IBS was specific to this condition or found in all types of D-IBS.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: