Intestinal Permeability in Irritable Bowel Syndrome Patients: Effects of NSAIDs
Intestinal permeability and the effect of NSAIDs on permeability were investigated in 14 irritable bowel syndrome (IBS) patients and 15 healthy subjects. In the study, 24-h urinary recoveries of orally administered polyethylene glycols (PEGs 400, 1500, and 4000) were not significantly different in healthy subjects and IBS patients before or after NSAID ingestion. Lactulose mannitol ratios in healthy subjects and IBS patients were not significantly different. Only time-dependent monitoring of PEG excretion showed that NSAIDs enhanced intestinal permeability for PEG 4000 in healthy subjects (P = 0.050) and for PEGs 400, 1500, and 4000 in IBS patients (P = 0.012, P = 0.041, and P = 0.012, respectively). These results show that intestinal permeability in IBS patients is not different from that in healthy subjects; NSAIDs compromise intestinal permeability in IBS patients to a greater extent than in healthy subjects, which suggests that IBS is associated with an altered response of the intestinal barrier to noxious agents.
KeywordsNSAIDs Polyethylene glycol PEG Intestinal permeability IBS
We acknowledge the staff of the Department of Pharmacy of the UMC Utrecht for production and supply of PEG and L/M test solutions. We thank M. van Loon, BSc, R. Voorbij, PhD, and coworkers of the Central Diagnostic Laboratory of the UMC Utrecht for the measurements of lactulose, mannitol, and creatinine. This work was funded in part by a Gastrostart grant from the Netherlands Society of Gastroenterology. APM Kerckhoffs was financially supported by Numico Research BV. LMA Akkermans received financial support from AstraZeneca R&D, Mölndal, Sweden. Supporting institutions were not involved in design, performance, or publication of this study.
- 4.Spiller RC, Jenkins D, Thornley JP, et al. 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(6):804–811. doi:10.1136/gut.47.6.804.CrossRefPubMedGoogle Scholar
- 5.Marshall JK, Thabane M, Garg AX, Clark W, Meddings J, Collins SM. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther. 2004;20(11–12):1317–1322. doi:10.1111/j.1365-2036.2004.02284.x.CrossRefPubMedGoogle Scholar
- 13.Kalantar JS, Locke GR III, Talley NJ, Zinsmeister AR, Fett SL, Melton LJ III. Is irritable bowel syndrome more likely to be persistent in those with relatives who suffer from gastrointestinal symptoms? A population-based study at three time points. Aliment Pharmacol Ther. 2003;17(11):1389–1397. doi:10.1046/j.1365-2036.2003.01591.x.CrossRefPubMedGoogle Scholar
- 23.Parlesak A, Schafer C, Schutz T, Bode JC, Bode C. Increased intestinal permeability to macromolecules and endotoxemia in patients with chronic alcohol abuse in different stages of alcohol-induced liver disease. J Hepatol. 2000;32(5):742–747. doi:10.1016/S0168-8278(00)80242-1.CrossRefPubMedGoogle Scholar
- 26.Kanda T, Fujii H, Fujita M, Sakai Y, Ono T, Hatakeyama K. Intestinal fatty acid binding protein is available for diagnosis of intestinal ischaemia: immunochemical analysis of two patients with ischaemic intestinal diseases. Gut. 1995;36(5):788–791. doi:10.1136/gut.36.5.788.CrossRefPubMedGoogle Scholar
- 48.Somasundaram S, Sigthorsson G, Simpson RJ, et al. Uncoupling of intestinal mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase are required for the development of NSAID-enteropathy in the rat. Aliment Pharmacol Ther. 2000;14(5):639–650. doi:10.1046/j.1365-2036.2000.00723.x.CrossRefPubMedGoogle Scholar