Home LiteratureArticle Details
PMID: 27763627 Published · epublish English Review Journal Article

Human Intestinal Barrier Function in Health and Disease.

Clinical and translational gastroenterology ·Vol. 7 ·No. 10 ·2016-10-20 ·Pages e196

König J, Wells J, Cani PD, García-Ródenas CL, MacDonald T, Mercenier A, Whyte J, Troost F, Brummer RJ

Abstract

The gastrointestinal tract consists of an enormous surface area that is optimized to efficiently absorb nutrients, water, and electrolytes from food. At the same time, it needs to provide a tight barrier against the ingress of harmful substances, and protect against a reaction to omnipresent harmless compounds. A dysfunctional intestinal barrier is associated with various diseases and disorders. In this review, the role of intestinal permeability in common disorders such as infections with intestinal pathogens, inflammatory bowel disease, irritable bowel syndrome, obesity, celiac disease, non-celiac gluten sensitivity, and food allergies will be discussed. In addition, the effect of the frequently prescribed drugs proton pump inhibitors and non-steroidal anti-inflammatory drugs on intestinal permeability, as well as commonly used methods to assess barrier function will be reviewed.

Authors & Affiliations
9 authors, click to expand affiliations / ORCID
König Julia
Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
Wells Jerry
Host-Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Cani Patrice D
Metabolism and Nutrition Research Group, WELBIO-Walloon Excellence in Life Sciences and BIOtechnology, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, Belgium.
García-Ródenas Clara L
Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
MacDonald Tom
Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Mercenier Annick
Nutrition and Health Research, Nestlé Research Center, Lausanne, Switzerland.
Whyte Jacqueline
European Branch, The International Life Sciences Institute, Brussels, Belgium.
Troost Freddy
Division of Gastroenterology-Hepatology, Department of Internal Medicine, University Hospital Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
Brummer Robert-Jan
Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden.
References (186)
186 references, click to expand
  1. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives.
    J Pediatr Gastroenterol Nutr. 2010 Oct;51(4):418-24 PMID: 20683204
  2. Mucosal flora in inflammatory bowel disease.
    Gastroenterology. 2002 Jan;122(1):44-54 PMID: 11781279
  3. Epithelial NEMO links innate immunity to chronic intestinal inflammation.
    Nature. 2007 Mar 29;446(7135):557-61 PMID: 17361131
  4. Muc2-deficient mice spontaneously develop colitis, indicating that MUC2 is critical for colonic protection.
    Gastroenterology. 2006 Jul;131(1):117-29 PMID: 16831596
  5. Proton pump inhibitors: actions and reactions.
    Drug Discov Today. 2009 Jul;14(13-14):647-60 PMID: 19443264
  6. Gastrointestinal profile of symptomatic athletes at rest and during physical exercise.
    Eur J Appl Physiol. 2004 Apr;91(4):429-34 PMID: 14634826
  7. Pathogenic Escherichia coli.
    Nat Rev Microbiol. 2004 Feb;2(2):123-40 PMID: 15040260
  8. Dietary emulsifiers impact the mouse gut microbiota promoting colitis and metabolic syndrome.
    Nature. 2015 Mar 5;519(7541):92-6 PMID: 25731162
  9. The rotavirus surface protein VP8 modulates the gate and fence function of tight junctions in epithelial cells.
    J Cell Sci. 2004 Nov 1;117(Pt 23):5509-19 PMID: 15494377
  10. Specific H+/K(+)-ATPase inhibitors decreased contractile responses of isolated rat vas deferens.
    Pharmacol Res. 2006 Dec;54(6):397-405 PMID: 16949299
  11. Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
    Nat Genet. 2011 Mar;43(3):246-52 PMID: 21297633
  12. Intestinal barrier dysfunction by enteropathogenic Escherichia coli is mediated by two effector molecules and a bacterial surface protein.
    Mol Microbiol. 2004 Nov;54(3):665-75 PMID: 15491358
  13. Mechanisms underlying intestinal injury induced by anti-inflammatory COX inhibitors.
    Eur J Pharmacol. 2004 Oct 1;500(1-3):427-39 PMID: 15464050
  14. Omeprazole increases permeability across isolated rat gastric mucosa pre-treated with an acid secretagogue.
    J Pharm Pharmacol. 2002 Mar;54(3):341-7 PMID: 11902800
  15. Endotoxemia is associated with an increased risk of incident diabetes.
    Diabetes Care. 2011 Feb;34(2):392-7 PMID: 21270197
  16. Rapid disruption of intestinal barrier function by gliadin involves altered expression of apical junctional proteins.
    FEBS Lett. 2005 Aug 29;579(21):4851-5 PMID: 16099460
  17. Anxiety and depression comorbidities in irritable bowel syndrome (IBS): a systematic review and meta-analysis.
    Eur Arch Psychiatry Clin Neurosci. 2014 Dec;264(8):651-60 PMID: 24705634
  18. Endotoxins in liver disease.
    Gastroenterology. 1978 Oct;75(4):765-6 PMID: 710846
  19. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome.
    Pain. 2009 Nov;146(1-2):41-6 PMID: 19595511
  20. Soluble mediators released from PI-IBS patients' colon induced alteration of mast cell: involvement of reactive oxygen species.
    Dig Dis Sci. 2012 Feb;57(2):311-9 PMID: 21901252
  21. COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice.
    Gastroenterology. 2002 Jun;122(7):1913-23 PMID: 12055598
  22. Energy intake is associated with endotoxemia in apparently healthy men.
    Am J Clin Nutr. 2008 May;87(5):1219-23 PMID: 18469242
  23. Claudin-2, a component of the tight junction, forms a paracellular water channel.
    J Cell Sci. 2010 Jun 1;123(Pt 11):1913-21 PMID: 20460438
  24. Intestinal permeability--a new target for disease prevention and therapy.
    BMC Gastroenterol. 2014 Nov 18;14:189 PMID: 25407511
  25. Interleukin-10-deficient mice develop chronic enterocolitis.
    Cell. 1993 Oct 22;75(2):263-74 PMID: 8402911
  26. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.
    Gastroenterology. 2008 Jul;135(1):194-204.e3 PMID: 18485912
  27. Early effects of gliadin on enterocyte intracellular signalling involved in intestinal barrier function.
    Gut. 2003 Feb;52(2):218-23 PMID: 12524403
  28. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines.
    Scand J Gastroenterol. 2006 Apr;41(4):408-19 PMID: 16635908
  29. Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal anti-inflammatory drugs.
    Lancet. 1984 Nov 24;2(8413):1171-4 PMID: 6150232
  30. Proton pump inhibitor use is associated with an increased risk for microscopic colitis: a case-control study.
    Aliment Pharmacol Ther. 2010 Nov;32(9):1124-8 PMID: 21039674
  31. Helicobacter pylori alters the distribution of ZO-1 and p120ctn in primary human gastric epithelial cells.
    Pathol Res Pract. 2007;203(6):433-44 PMID: 17509776
  32. Novel opportunities for next-generation probiotics targeting metabolic syndrome.
    Curr Opin Biotechnol. 2015 Apr;32:21-7 PMID: 25448228
  33. Regulation of epithelial tight junction assembly and disassembly by AMP-activated protein kinase.
    Proc Natl Acad Sci U S A. 2007 Jan 16;104(3):819-22 PMID: 17204563
  34. Esomeprazole induces upper gastrointestinal tract transmucosal permeability increase.
    Aliment Pharmacol Ther. 2008 Dec 1;28(11-12):1317-25 PMID: 18684245
  35. Contribution of the IBD5 locus to inflammatory bowel disease: a meta-analysis.
    Hum Genet. 2011 Jun;129(6):597-609 PMID: 21279723
  36. Epithelial tight junction structure in the jejunum of children with acute and treated celiac sprue.
    Pediatr Res. 1998 Apr;43(4 Pt 1):435-41 PMID: 9544995
  37. Functional bowel disorders and irritable bowel syndrome in Europe.
    Aliment Pharmacol Ther. 2003 Nov;18 Suppl 3:75-9 PMID: 14531746
  38. Autoimmune diseases, gastrointestinal disorders and the microbiome in schizophrenia: more than a gut feeling.
    Schizophr Res. 2016 Sep;176(1):23-35 PMID: 25034760
  39. Enteropathogenic Escherichia coli activates ezrin, which participates in disruption of tight junction barrier function.
    Infect Immun. 2001 Sep;69(9):5679-88 PMID: 11500444
  40. Depression, anxiety, and the gastrointestinal system.
    J Clin Psychiatry. 2001;62 Suppl 8:28-36; discussion 37 PMID: 12108819
  41. An Update on Post-infectious Irritable Bowel Syndrome: Role of Genetics, Immune Activation, Serotonin and Altered Microbiome.
    J Neurogastroenterol Motil. 2012 Jul;18(3):258-68 PMID: 22837873
  42. So depression is an inflammatory disease, but where does the inflammation come from?
    BMC Med. 2013 Sep 12;11:200 PMID: 24228900
  43. Acute gastrointestinal permeability responses to different non-steroidal anti-inflammatory drugs.
    Gut. 2001 Nov;49(5):650-5 PMID: 11600467
  44. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis.
    Gut. 2012 Sep;61(9):1355-64 PMID: 21890812
  45. Increase in plasma endotoxin concentrations and the expression of Toll-like receptors and suppressor of cytokine signaling-3 in mononuclear cells after a high-fat, high-carbohydrate meal: implications for insulin resistance.
    Diabetes Care. 2009 Dec;32(12 ):2281-7 PMID: 19755625
  46. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene.
    Science. 2006 Dec 1;314(5804):1461-3 PMID: 17068223
  47. Intestinal epithelial MyD88 is a sensor switching host metabolism towards obesity according to nutritional status.
    Nat Commun. 2014 Dec 05;5:5648 PMID: 25476696
  48. 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 May;14(5):639-50 PMID: 10792129
  49. The whole Shebang: the gastrointestinal tract, Escherichia coli enterotoxins and secretion.
    Curr Issues Mol Biol. 2012;14(2):71-82 PMID: 22368232
  50. Multistep entry of rotavirus into cells: a Versaillesque dance.
    Trends Microbiol. 2004 Jun;12(6):271-8 PMID: 15165605
  51. Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD.
    Am J Physiol Cell Physiol. 2004 Oct;287(4):C939-48 PMID: 15175224
  52. Effect of running intensity on intestinal permeability.
    J Appl Physiol (1985). 1997 Feb;82(2):571-6 PMID: 9049739
  53. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease.
    Lancet. 2000 Apr 29;355(9214):1518-9 PMID: 10801176
  54. The active Zot domain (aa 288-293) increases ZO-1 and myosin 1C serine/threonine phosphorylation, alters interaction between ZO-1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation.
    FASEB J. 2011 Jan;25(1):144-58 PMID: 20852064
  55. A high-fat meal induces low-grade endotoxemia: evidence of a novel mechanism of postprandial inflammation.
    Am J Clin Nutr. 2007 Nov;86(5):1286-92 PMID: 17991637
  56. Purification of a 20 kDa phosphoprotein from epithelial cells and identification as a myosin light chain. Phosphorylation induced by enteropathogenic Escherichia coli and phorbol ester.
    FEBS Lett. 1991 Nov 4;292(1-2):121-7 PMID: 1959591
  57. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators.
    Gut. 2009 Feb;58(2):196-201 PMID: 18824556
  58. Escherichia coli STb toxin and colibacillosis: knowing is half the battle.
    FEMS Microbiol Lett. 2008 Jan;278(2):137-45 PMID: 17995951
  59. Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation.
    Gastroenterology. 1997 Jan;112(1):109-17 PMID: 8978349
  60. 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 Jan;56(1):61-72 PMID: 16822808
  61. Mitochondrial damage: a possible mechanism of the "topical" phase of NSAID induced injury to the rat intestine.
    Gut. 1997 Sep;41(3):344-53 PMID: 9378390
  62. The role of epithelial malfunction in the pathogenesis of enteropathogenic E. coli-induced diarrhea.
    Lab Invest. 2009 Sep;89(9):964-70 PMID: 19620958
  63. Oxidative stress-induced disruption of epithelial and endothelial tight junctions.
    Front Biosci. 2008 May 01;13:7210-26 PMID: 18508729
  64. Susceptibility to gut leakiness: a possible mechanism for endotoxaemia in non-alcoholic steatohepatitis.
    Liver Int. 2008 Aug;28(7):1026-33 PMID: 18397235
  65. Structure-function analysis of reovirus binding to junctional adhesion molecule 1. Implications for the mechanism of reovirus attachment.
    J Biol Chem. 2003 Nov 28;278(48):48434-44 PMID: 12966102
  66. Mechanism of IL-1β modulation of intestinal epithelial barrier involves p38 kinase and activating transcription factor-2 activation.
    J Immunol. 2013 Jun 15;190(12):6596-606 PMID: 23656735
  67. Increased intestinal permeability and tight junction alterations in nonalcoholic fatty liver disease.
    Hepatology. 2009 Jun;49(6):1877-87 PMID: 19291785
  68. Macrophages, inflammation, and insulin resistance.
    Annu Rev Physiol. 2010;72:219-46 PMID: 20148674
  69. Clinicopathological features of nonsteroidal antiinflammatory drug-induced small intestinal strictures.
    Gastroenterology. 1988 Apr;94(4):1070-4 PMID: 3345876
  70. Small-intestinal function during enteral feeding and starvation in man.
    Clin Sci (Lond). 1989 Oct;77(4):401-6 PMID: 2509127
  71. Faecalibacterium prausnitzii and human intestinal health.
    Curr Opin Microbiol. 2013 Jun;16(3):255-61 PMID: 23831042
  72. Non-steroidal anti-inflammatory drug induced injury to the small intestine.
    Acta Medica (Hradec Kralove). 2010;53(1):3-11 PMID: 20608226
  73. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity.
    Nutrients. 2015 Feb 27;7(3):1565-76 PMID: 25734566
  74. Mechanism of action of ZOT-derived peptide AT-1002, a tight junction regulator and absorption enhancer.
    Int J Pharm. 2009 Jan 5;365(1-2):121-30 PMID: 18832018
  75. Prevalence of and risk factors for nonalcoholic fatty liver disease: the Dionysos nutrition and liver study.
    Hepatology. 2005 Jul;42(1):44-52 PMID: 15895401
  76. Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes.
    Am J Physiol Endocrinol Metab. 2007 Mar;292(3):E740-7 PMID: 17090751
  77. Enteroaggregative Escherichia coli (EAEC): a cause of acute and persistent diarrhea of worldwide importance.
    J Infect Dis. 2010 Aug 15;202(4):503-5 PMID: 20594108
  78. Functional dysbiosis within the gut microbiota of patients with constipated-irritable bowel syndrome.
    Aliment Pharmacol Ther. 2012 Apr;35(7):828-38 PMID: 22315951
  79. Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA.
    Science. 2003 May 30;300(5624):1430-4 PMID: 12775840
  80. Effects of oral adenosine 5'-triphosphate and adenosine in enteric-coated capsules on indomethacin-induced permeability changes in the human small intestine: a randomized cross-over study.
    BMC Gastroenterol. 2007 Jun 19;7:23 PMID: 17578566
  81. Corticotropin-releasing factor receptor 1 antagonist alters regional activation and effective connectivity in an emotional-arousal circuit during expectation of abdominal pain.
    J Neurosci. 2011 Aug 31;31(35):12491-500 PMID: 21880911
  82. Colonic mucin synthesis is increased by sodium butyrate.
    Gut. 1995 Jan;36(1):93-9 PMID: 7890244
  83. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier.
    Am J Physiol Gastrointest Liver Physiol. 2010 Jun;298(6):G851-9 PMID: 20224007
  84. Inflammatory bowel disease and adenomas in mice expressing a dominant negative N-cadherin.
    Science. 1995 Nov 17;270(5239):1203-7 PMID: 7502046
  85. Short report: the effect of misoprostol on the anaemia of NSAID enteropathy.
    Aliment Pharmacol Ther. 1994 Jun;8(3):343-6 PMID: 7918931
  86. Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress.
    Aliment Pharmacol Ther. 2015 Feb;41(4):342-51 PMID: 25521822
  87. Caspase-8 regulates TNF-α-induced epithelial necroptosis and terminal ileitis.
    Nature. 2011 Sep 14;477(7364):335-9 PMID: 21921917
  88. Republished: bacterial proteases in IBD and IBS.
    Postgrad Med J. 2013 Jan;89(1047):25-33 PMID: 23257716
  89. Effects of metronidazole and misoprostol on indomethacin-induced changes in intestinal permeability.
    Dig Dis Sci. 1993 Mar;38(3):417-25 PMID: 8444070
  90. Clinical Implications of Histologic Abnormalities in Ileocolonic Biopsies of Patients With Crohn's Disease in Remission.
    J Clin Gastroenterol. 2017 Jan;51(1):43-48 PMID: 26927490
  91. Increased IgA and IgM responses against gut commensals in chronic depression: further evidence for increased bacterial translocation or leaky gut.
    J Affect Disord. 2012 Dec 1;141(1):55-62 PMID: 22410503
  92. Colitis in chronic granulomatous disease.
    Arch Dis Child. 2001 Feb;84(2):147-51 PMID: 11159292
  93. Obesity.
    Circulation. 2005 Apr 19;111(15):e257-9 PMID: 15837935
  94. Escherichia coli heat-stable toxin b impairs intestinal epithelial barrier function by altering tight junction proteins.
    Infect Immun. 2013 Aug;81(8):2819-27 PMID: 23716609
  95. Loss of hepatocyte-nuclear-factor-4alpha affects colonic ion transport and causes chronic inflammation resembling inflammatory bowel disease in mice.
    PLoS One. 2009 Oct 29;4(10):e7609 PMID: 19898610
  96. Helicobacter pylori CagA induces a transition from polarized to invasive phenotypes in MDCK cells.
    Proc Natl Acad Sci U S A. 2005 Nov 8;102(45):16339-44 PMID: 16258069
  97. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome.
    Gastroenterology. 2011 Nov;141(5):1792-801 PMID: 21820992
  98. Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions.
    Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5242-6 PMID: 2052603
  99. TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1.
    Am J Pathol. 2013 Dec;183(6):1871-84 PMID: 24121020
  100. Post-infectious irritable bowel syndrome: the past, the present and the future.
    J Gastroenterol Hepatol. 2011 Apr;26 Suppl 3:94-101 PMID: 21443719
  101. The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn's disease.
    Gastroenterology. 2005 Dec;129(6):1854-64 PMID: 16344054
  102. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.
    Proc Natl Acad Sci U S A. 2013 May 28;110(22):9066-71 PMID: 23671105
  103. Salmonella enterica serovar Typhimurium effectors SopB, SopE, SopE2 and SipA disrupt tight junction structure and function.
    Cell Microbiol. 2006 Dec;8(12):1946-57 PMID: 16869830
  104. Changes in gut microbiota control metabolic endotoxemia-induced inflammation in high-fat diet-induced obesity and diabetes in mice.
    Diabetes. 2008 Jun;57(6):1470-81 PMID: 18305141
  105. The role of endotoxin in liver injury.
    Gastroenterology. 1975 Dec;69(6):1346-56 PMID: 1104401
  106. Immunohistochemical analysis of ZO-1 in the duodenal mucosa of patients with untreated and treated celiac disease.
    Digestion. 2002;65(4):227-33 PMID: 12239464
  107. Review article: the role of butyrate on colonic function.
    Aliment Pharmacol Ther. 2008 Jan 15;27(2):104-19 PMID: 17973645
  108. Misoprostol reduces indomethacin-induced changes in human small intestinal permeability.
    Dig Dis Sci. 1989 Mar;34(3):407-11 PMID: 2493366
  109. Mucosal cytokine response after short-term gluten challenge in celiac disease and non-celiac gluten sensitivity.
    Am J Gastroenterol. 2013 May;108(5):842-50 PMID: 23588237
  110. Local effect of adenosine 5'-triphosphate on indomethacin-induced permeability changes in the human small intestine.
    Eur J Gastroenterol Hepatol. 2007 Mar;19(3):245-50 PMID: 17301652
  111. Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro.
    Gut. 2008 Jan;57(1):50-8 PMID: 17525093
  112. The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice.
    Gastroenterology. 2004 Jul;127(1):94-104 PMID: 15236176
  113. Specific nongluten proteins of wheat are novel target antigens in celiac disease humoral response.
    J Proteome Res. 2015 Jan 2;14(1):503-11 PMID: 25329597
  114. Cellular and molecular mechanisms underlying NOD2 risk-associated polymorphisms in Crohn's disease.
    Immunol Rev. 2014 Jul;260(1):249-60 PMID: 24942694
  115. TNFalpha up-regulates claudin-2 expression in epithelial HT-29/B6 cells via phosphatidylinositol-3-kinase signaling.
    Cell Tissue Res. 2009 Apr;336(1):67-77 PMID: 19214581
  116. Modulation of tight junction structure and function by kinases and phosphatases targeting occludin.
    J Biomed Biotechnol. 2012;2012:807356 PMID: 22315516
  117. A guide to Ussing chamber studies of mouse intestine.
    Am J Physiol Gastrointest Liver Physiol. 2009 Jun;296(6):G1151-66 PMID: 19342508
  118. NSAID-induced intestinal damage: are luminal bacteria the therapeutic target?
    Gut. 2008 Feb;57(2):145-8 PMID: 18192448
  119. Omeprazole induces gastric transmucosal permeability to the peptide bradykinin.
    World J Gastroenterol. 2010 Mar 7;16(9):1097-103 PMID: 20205280
  120. Genetic variants in TNF-alpha but not DLG5 are associated with inflammatory bowel disease in a large United Kingdom cohort.
    Inflamm Bowel Dis. 2006 Mar;12 (3):178-84 PMID: 16534418
  121. Aberrant mucin assembly in mice causes endoplasmic reticulum stress and spontaneous inflammation resembling ulcerative colitis.
    PLoS Med. 2008 Mar 4;5(3):e54 PMID: 18318598
  122. Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders.
    Aliment Pharmacol Ther. 2014 Aug;40(3):288-97 PMID: 24943095
  123. A persistent defect in intestinal permeability in coeliac disease demonstrated by a 51Cr-labelled EDTA absorption test.
    Lancet. 1983 Feb 12;1(8320):323-5 PMID: 6130333
  124. XBP1 links ER stress to intestinal inflammation and confers genetic risk for human inflammatory bowel disease.
    Cell. 2008 Sep 5;134(5):743-56 PMID: 18775308
  125. Differential expression of toll-like receptors in patients with irritable bowel syndrome.
    Am J Gastroenterol. 2011 Feb;106(2):329-36 PMID: 21102570
  126. Pilot study: alterations of intestinal microbiota in obese humans are not associated with colonic inflammation or disturbances of barrier function.
    Aliment Pharmacol Ther. 2010 Dec;32(11-12):1307-14 PMID: 21050232
  127. Intestinal permeability in patients with adverse reactions to food.
    Dig Liver Dis. 2006 Oct;38(10):732-6 PMID: 16880015
  128. Cryptogenic multifocal ulcerating stenosing enteritis associated with homozygous deletion mutations in cytosolic phospholipase A2-α.
    Gut. 2014 Jan;63(1):96-104 PMID: 23268370
  129. Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity.
    BMC Med. 2011 Mar 09;9:23 PMID: 21392369
  130. Innate immunity modulates adipokines in humans.
    J Clin Endocrinol Metab. 2007 Jun;92(6):2272-9 PMID: 17374708
  131. Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens.
    FEMS Microbiol Rev. 2004 Oct;28(4):405-40 PMID: 15374659
  132. Use of anti-inflammatory drugs by patients admitted with small or large bowel perforations and haemorrhage.
    Br Med J (Clin Res Ed). 1985 Feb 2;290(6465):347-9 PMID: 3917814
  133. Enteropathogenic Escherichia coli infection leads to appearance of aberrant tight junctions strands in the lateral membrane of intestinal epithelial cells.
    Cell Microbiol. 2004 Aug;6(8):783-93 PMID: 15236645
  134. Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers.
    Eur J Clin Nutr. 2003 Dec;57(12):1579-85 PMID: 14647223
  135. Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review.
    J Gastroenterol. 2011 Apr;46(4):421-31 PMID: 21331765
  136. Attaching effacing Escherichia coli and paradigms of Tir-triggered actin polymerization: getting off the pedestal.
    Cell Microbiol. 2008 Mar;10(3):549-56 PMID: 18053003
  137. Measurement of intestinal permeability to mannitol and lactulose as a means of diagnosing food allergy and evaluating therapeutic effectiveness of disodium cromoglycate.
    Ann Allergy. 1987 Nov;59(5 Pt 2):127-30 PMID: 3120628
  138. Differential effects of cream, glucose, and orange juice on inflammation, endotoxin, and the expression of Toll-like receptor-4 and suppressor of cytokine signaling-3.
    Diabetes Care. 2010 May;33(5):991-7 PMID: 20067961
  139. Intestinal permeability is associated with visceral adiposity in healthy women.
    Obesity (Silver Spring). 2011 Nov;19(11):2280-2 PMID: 21852815
  140. Enterohemorrhagic E. coli alters murine intestinal epithelial tight junction protein expression and barrier function in a Shiga toxin independent manner.
    Lab Invest. 2010 Aug;90(8):1152-68 PMID: 20479715
  141. Nonsteroidal antiinflammatory drugs and the small intestine.
    Curr Opin Gastroenterol. 2005 Mar;21(2):169-75 PMID: 15711208
  142. Discordant patterns of bacterial translocation markers and implications for innate immune imbalances in schizophrenia.
    Schizophr Res. 2013 Aug;148(1-3):130-7 PMID: 23746484
  143. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells.
    J Cell Sci. 2002 Dec 15;115(Pt 24):4969-76 PMID: 12432083
  144. Spectrum of gluten-related disorders: consensus on new nomenclature and classification.
    BMC Med. 2012 Feb 07;10:13 PMID: 22313950
  145. The commensal microbiota and enteropathogens in the pathogenesis of inflammatory bowel diseases.
    Gastroenterology. 2011 May;140(6):1720-28 PMID: 21530738
  146. Meta-analysis of probiotics for the prevention of traveler's diarrhea.
    Travel Med Infect Dis. 2007 Mar;5(2):97-105 PMID: 17298915
  147. Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis.
    N Engl J Med. 2003 Jul 24;349(4):350-7 PMID: 12878742
  148. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease.
    Nature. 2001 May 31;411(6837):599-603 PMID: 11385576
  149. Transmucosal gastric leak induced by proton pump inhibitors.
    Dig Dis Sci. 2009 Jul;54(7):1408-17 PMID: 19015985
  150. Alteration of the intestinal microbiota as a cause of and a potential therapeutic option in irritable bowel syndrome.
    Benef Microbes. 2014 Sep;5(3):247-61 PMID: 24583610
  151. The leaky gut of alcoholism: possible route of entry for toxic compounds.
    Lancet. 1984 Jan 28;1(8370):179-82 PMID: 6141332
  152. Relaxant effect of omeprazole and lansoprazole in guinea pig gallbladder muscle strips in vitro.
    J Gastroenterol. 2003;38(8):765-71 PMID: 14505131
  153. A phosphorylation hotspot within the occludin C-terminal domain.
    Ann N Y Acad Sci. 2012 Jun;1257:38-44 PMID: 22671587
  154. Intestinal permeability in children with food allergy on specific elimination diets.
    Pediatr Allergy Immunol. 2013 Sep;24(6):589-95 PMID: 23909601
  155. Ulcerative colitis-risk loci on chromosomes 1p36 and 12q15 found by genome-wide association study.
    Nat Genet. 2009 Feb;41(2):216-20 PMID: 19122664
  156. Butyrate modulates oxidative stress in the colonic mucosa of healthy humans.
    Clin Nutr. 2009 Feb;28(1):88-93 PMID: 19108937
  157. Blood and protein loss via small-intestinal inflammation induced by non-steroidal anti-inflammatory drugs.
    Lancet. 1987 Sep 26;2(8561):711-4 PMID: 2888943
  158. Intestinal permeability in patients with coeliac disease and relatives of patients with coeliac disease.
    Gut. 1993 Mar;34(3):354-7 PMID: 8472983
  159. Altered peripheral toll-like receptor responses in the irritable bowel syndrome.
    Aliment Pharmacol Ther. 2011 May;33(9):1045-52 PMID: 21453321
  160. A claudin 3 and claudin 4-targeted Clostridium perfringens protoxin is selectively cytotoxic to PSA-producing prostate cancer cells.
    Cancer Lett. 2014 Sep 1;351(2):260-4 PMID: 24952257
  161. Psychosocial aspects of the functional gastrointestinal disorders.
    Gastroenterology. 2006 Apr;130(5):1447-58 PMID: 16678558
  162. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome.
    Gut. 2010 Jun;59(6):775-84 PMID: 19951903
  163. Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet.
    Dig Liver Dis. 2004 May;36(5):337-41 PMID: 15191203
  164. Present status and strategy of NSAIDs-induced small bowel injury.
    J Gastroenterol. 2009;44(9):879-88 PMID: 19568687
  165. Physiological regulation of epithelial tight junctions is associated with myosin light-chain phosphorylation.
    Am J Physiol. 1997 Oct;273(4 Pt 1):C1378-85 PMID: 9357784
  166. RIPK1 ensures intestinal homeostasis by protecting the epithelium against apoptosis.
    Nature. 2014 Sep 4;513(7516):95-9 PMID: 25186904
  167. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy.
    J Gastroenterol. 2009;44 Suppl 19:23-9 PMID: 19148789
  168. Inflammatory bowel disease and mutations affecting the interleukin-10 receptor.
    N Engl J Med. 2009 Nov 19;361(21):2033-45 PMID: 19890111
  169. IL-22-STAT3 pathway plays a key role in the maintenance of ileal homeostasis in mice lacking secreted mucus barrier.
    Inflamm Bowel Dis. 2015 Mar;21(3):531-42 PMID: 25636123
  170. Gut permeability and food allergies.
    Clin Exp Allergy. 2011 Jan;41(1):20-8 PMID: 21070397
  171. Importance of disrupted intestinal barrier in inflammatory bowel diseases.
    Inflamm Bowel Dis. 2011 Jan;17(1):362-81 PMID: 20725949
  172. Intestinal permeability changes in response to acetylsalicylic acid in relatives of patients with Crohn's disease.
    Gastroenterology. 1996 May;110(5):1395-403 PMID: 8613043
  173. Omeprazole induces gastric permeability to digoxin.
    Dig Dis Sci. 2010 May;55(5):1255-63 PMID: 19513837
  174. Gastrointestinal microbiome signatures of pediatric patients with irritable bowel syndrome.
    Gastroenterology. 2011 Nov;141(5):1782-91 PMID: 21741921
  175. Metabolic endotoxemia initiates obesity and insulin resistance.
    Diabetes. 2007 Jul;56(7):1761-72 PMID: 17456850
  176. The endocannabinoid system links gut microbiota to adipogenesis.
    Mol Syst Biol. 2010 Jul;6:392 PMID: 20664638
  177. Novel insights in the role of peripheral corticotropin-releasing factor and mast cells in stress-induced visceral hypersensitivity.
    Neurogastroenterol Motil. 2012 Mar;24(3):201-5 PMID: 22316289
  178. Comparative analysis of EspF from enteropathogenic and enterohemorrhagic Escherichia coli in alteration of epithelial barrier function.
    Infect Immun. 2004 Jun;72(6):3218-27 PMID: 15155623
  179. Cytokines induce tight junction disassembly in airway cells via an EGFR-dependent MAPK/ERK1/2-pathway.
    Lab Invest. 2012 Aug;92(8):1140-8 PMID: 22584669
  180. A role for intracellular calcium in tight junction reassembly after ATP depletion-repletion.
    Am J Physiol. 1999 Oct;277(4 Pt 2):F524-32 PMID: 10516276
  181. Effect of non-steroidal anti-inflammatory drugs and prostaglandins on the permeability of the human small intestine.
    Gut. 1986 Nov;27(11):1292-7 PMID: 3466837
  182. Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism.
    Gut. 2014 Aug;63(8):1293-9 PMID: 24153250
  183. Emulsified lipids increase endotoxemia: possible role in early postprandial low-grade inflammation.
    J Nutr Biochem. 2011 Jan;22(1):53-9 PMID: 20303729
  184. Changes in endotoxin levels in T2DM subjects on anti-diabetic therapies.
    Cardiovasc Diabetol. 2009 Apr 15;8:20 PMID: 19368716
  185. Novel multi-sugar assay for site-specific gastrointestinal permeability analysis: a randomized controlled crossover trial.
    Clin Nutr. 2013 Apr;32(2):245-51 PMID: 22892368
  186. Intestinal permeability in long-term follow-up of patients with celiac disease on a gluten-free diet.
    Dig Dis Sci. 2005 Apr;50(4):785-90 PMID: 15844719
Article Info
Journal
Clinical and translational gastroenterology
Abbr.
Clin Transl Gastroenterol
ISSN
2155-384X
DOI
10.1038/ctg.2016.54
Published
2016-10-20
Epub
2016-00-20
Pages
e196
Language
English
Region
United States
NLM ID
101532142
PMCID
PMC5288588
External Links
PubMed source DOI: 10.1038/ctg.2016.54 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2