Background/Aims: Defective epithelial barrier has been implicated in the pathogenesis of irritable bowel syndrome (IBS) and inflammatory bowel diseases. The aim of this study was to investigate gut permeability in patients with inactive ulcerative colitis (UC) and in patients with IBS. Methods: IBS patients of the diarrhea-predominant (IBS-D) and of the constipation-predominant subgroup (IBS-C), patients with inactive UC and healthy subjects were enrolled. Gut permeability was evaluated by measuring 24-hour urine excretion of orally administered 51Cr-EDTA. Clinical symptoms were evaluated in IBS-D patients and correlated to colonic permeability. Results: There was a significant decrease in the proximal small intestinal permeability in IBS-C patients compared to controls (0.26 ± 0.05 vs. 0.63 ± 0.1%; p < 0.05). Distal small intestinal permeability showed no significant difference in the studied group of patients compared to controls. Colonic permeability of IBS-D and inactive UC patients was significantly increased compared to controls (2.68 ± 0.35 and 3.74 ± 0.49 vs. 1.04 ± 0.18%; p < 0.05, p < 0.001). Colonic permeability of IBS-D patients correlated with stool frequency. Conclusions: Elevated gut permeability is localized to the colon both in IBS-D and in inactive UC patients.

1.
Chadwick VS, Chen W, Shu D, Paulus B, Bethwaite P, Tie A, Wilson I: Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology 2002;122:1778–1783.
[PubMed]
2.
Barbara G, Stanghellini V, De Georgio R, Cremon C, Cottrell GS, Santini D, Pasquinelli G, Morselli-Labate AM, Grady EF, Bunnett NW, Collins SM, Corinaldesi R: Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004;126:693–702.
[PubMed]
3.
Park JH, Rhee PL, Kim HS, Lee JH, Kim YH, Kim JJ, Rhee JC: Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol 2006;21:71–78.
[PubMed]
4.
Tornblom H, Lindberg G, Nyberg B, Veress B: Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology 2002;123:1972–1979.
[PubMed]
5.
Porras M, Martín MT, Yang PC, Jury J, Perdue MH, Vergara P: Correlation between cyclical epithelial barrier dysfunction and bacterial translocation in the relapses of intestinal inflammation. Inflamm Bowel Dis 2006;12:843–852.
[PubMed]
6.
Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, Neal KR: Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000;47:804–811.
[PubMed]
7.
Dunlop SP, Hebden J, Campbell E, Naesdal J, Olbe L, Perkins AC, Spiller RC: Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006;101:1288–1294.
[PubMed]
8.
Zhou Q, Zhang B, Verne GN: Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009;146:41–46.
[PubMed]
9.
Marshall JK, Thabane M, Garg AX, Clark W, Meddings J, Collins SM, WEL Investigators: Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther 2004;20:1317–1322.
[PubMed]
10.
Piche T, Barbara G, Aubert P, Bruley des Varannes S, Dainese R, Nano JL, Cremon C, Stanghellini V, De Giorgio R, Galmiche JP, Neunlist M: Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 2009;58:196–201.
[PubMed]
11.
Jenkins RT, Ramage JK, Jones DB, Collins SM, Goodacre RL, Hunt RH: Small bowel and colonic permeability to 51Cr-EDTA in patients with active inflammatory bowel disease. Clin Invest Med 1988;11:151–155.
[PubMed]
12.
Söderholm JD, Peterson KH, Olaison G, Franzén LE, Weström B, Magnusson KE, Sjödahl R: Epithelial permeability to proteins in the noninflamed ileum of Crohn’s disease? Gastroenterology 1999;117:65–72.
[PubMed]
13.
Peeters M, Ghoos Y, Maes B, Hiele M, Geboes K, Vantrappen G, Rutgeerts P: Increased permeability of macroscopically normal small bowel in Crohn’s disease. Dig Dis Sci 1994;39:2170–2176.
[PubMed]
14.
Hollander D, Vadheim CM, Brettholz E, Petersen GM, Delahunty T, Rotter JI: Increased intestinal permeability in patients with Crohn’s disease and their relatives: a possible etiologic factor. Ann Intern Med 1986;105:883–885.
[PubMed]
15.
Wyatt J, Vogelsang H, Hübl W, Waldhöer T, Lochs H: Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 1993;341:1437–1439.
[PubMed]
16.
Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I: Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000;119:15–22.
[PubMed]
17.
Arslan G, Atasever T, Cindoruk M, Yildirim IS: (51)CrEDTA colonic permeability and therapy response in patients with ulcerative colitis. Nucl Med Commun 2001;22:997–1001.
[PubMed]
18.
Teahon K, Somasundaram S, Smith T, Menzies I, Bjarnason I: Assessing the site of increased intestinal permeability in coeliac and inflammatory bowel disease. Gut 1996;38:864–869.
[PubMed]
19.
Bjarnason I, Peters TJ, Veall N: A persistent defect in intestinal permeability in coeliac disease demonstrated by a 51Cr-labelled EDTA absorption test. Lancet 1983;i:323–325.
20.
Bjarnason I, O’Morain C, Levi AJ, Peters TJ: Absorption of 51chromium-labeled ethylenediaminetetraacetate in inflammatory bowel disease. Gastroenterology 1983;85:318–322.
[PubMed]
21.
McGuckin MA, Eri R, Simms LA, Florin TH, Radford-Smith G: Intestinal barrier dysfunction in inflammatory bowel diseases. Inflamm Bowel Dis 2009;15:100–113.
[PubMed]
22.
Gecse K, Róka R, Ferrier L, Leveque M, Eutamene H, Cartier C, Ait-Belgnaoui A, Rosztóczy A, Izbéki F, Fioramonti J, Wittmann T, Bueno L: Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic luminal factor impairing colonic permeability and sensitivity. Gut 2008;57:591–599.
[PubMed]
23.
Schmitz H, Barmeyer C, Fromm M, Runkel N, Foss HD, Bentzel CJ, Riecken EO, Schulzke JD: Altered tight junction structure contributes to the impaired epithelial barrier function in ulcerative colitis. Gastroenterology 1999;116:301–309.
[PubMed]
24.
Zeissig S, Bürgel N, Günzel D, et al: Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn’s disease. Gut 2007;56:61–72.
[PubMed]
25.
Róka R, Rosztóczy A, Leveque M, Izbéki F, Nagy F, Molnár T, Lonovics J, Garcia-Villar R, Fioramonti J, Wittmann T, Bueno L: A pilot study of fecal serine-protease activity: a pathophysiologic factor in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2007;5:550–555.
[PubMed]
26.
Kerckhoffs AP, Akkermans LM, de Smet MB, Besselink MG, Hietbrink F, Bartelink IH, Busschers WB, Samsom M, Renooij W: Intestinal permeability in irritable bowel syndrome patients: effects of NSAIDs. Dig Dis Sci 2010;55:716–723.
[PubMed]
27.
Camilleri M, Gorman H: Intestinal permeability and irritable bowel syndrome. Neurogastroenterol Motil 2007;19:545–552.
[PubMed]
28.
Philipsen EK, Batsberg W, Christensen AB: Gastrointestinal permeability to polyethylene glycol: an evaluation of urinary recovery of an oral load of polyethylene glycol as a parameter of intestinal permeability in man. Eur J Clin Invest 1988;18:139–145.
[PubMed]
29.
Jenkins AP, Nukajam WS, Menzies IS, Creamer B: Simultaneous administration of lactulose and 51Cr-ethylenediaminetetraacetic acid: a test to distinguish colonic from small-intestinal permeability change. Scand J Gastroenterol 1992;27:769–773.
[PubMed]
30.
Weston AP, Bidle WL, Bahtia PS, Minser PB: Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci 1993;38:1590–1595.
[PubMed]
31.
van Wijk HJ, Smout AJ, Akkermans LM, Roelofs JM, ten Thije OJ: Gastric emptying and dyspeptic symptoms in the irritable bowel syndrome. Scand J Gastroenterol 1992;27:99–102.
[PubMed]
32.
Shulman RJ, Eakin MN, Czyzewski DI, Jarrett M, Ou CN: Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008;153:646–650.
[PubMed]
33.
Gitter AH, Wullstein F, Fromm M, Schulzke JD: Epithelial barrier defects in ulcerative colitis: characterization and quantification by electrophysiological imaging. Gastroenterology 2001;121:1320–1328.
[PubMed]
34.
Sträter J, Wellisch I, Riedl S, Walczak H, Koretz K, Tandara A, Krammer PH, Möller P: CD95 (APO-1/Fas)-mediated apoptosis in colon epithelial cells: a possible role in ulcerative colitis. Gastroenterology 1997;113:160–167.
[PubMed]
35.
Blair SA, Kane SV, Clayburgh DR, Turner JR: Epithelial myosin light chain kinase expression and activity are upregulated in inflammatory bowel disease. Lab Invest 2006;86:191–201.
[PubMed]
36.
Dabek M, Ferrier L, Roka R, Gecse K, Annahazi A, Moreau J, Escourrou J, Cartier C, Chaumaz G, Leveque M, Ait-Belgnaoui A, Wittmann T, Theodorou V, Bueno L: Luminal cathepsin G and protease-activated receptor 4: a duet involved in alterations of the colonic epithelial barrier in ulcerative colitis. Am J Pathol 2009;175:207–214.
[PubMed]
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