Intestinal barrier function in health and gastrointestinal disease

Neurogastroenterology and Motility

Volumn 24, Issue 6, 2012, Pages 503-512

  Camilleri, M ^a   Madsen, K ^b   Spiller, R ^c   Van Meerveld, B G ^d   Verne, G N ^e  

^a Clinical Enteric Neuroscience Translational and Epidemiological Research Mayo Clinic   (United States)

^b UNIVERSITY OF ALBERTA   (Canada)

^c UNIVERSITY OF NOTTINGHAM   (United Kingdom)

^d UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

^e UNIVERSITY OF TEXAS MEDICAL BRANCH   (United States)

Author keywords

Glutamine; Intestinal barrier; Irritable bowel syndrome; MicroRNA; Tight junction proteins

Indexed keywords

ACTIN; CLAUDIN; CLAUDIN 1; CLAUDIN 10; CLAUDIN 2; CLAUDIN 3; CLAUDIN 4; CLAUDIN 5; CLAUDIN 7; CLAUDIN 8; GLUTAMATE AMMONIA LIGASE; GLUTAMINE; LACTULOSE; MANNITOL; MEMBRANE PROTEIN; OCCLUDIN; PROTEIN ZO1; PROTEIN ZO2; PROTEIN ZO3; SUCROSE; UNCLASSIFIED DRUG;

CELIAC DISEASE; ENTERITIS; EPITHELIUM; EXPERIMENTAL MODEL; GASTROENTERITIS; GASTROINTESTINAL DISEASE; GENETIC PREDISPOSITION; HEALTH; HUMAN; IMMUNOMODULATION; INTESTINE FUNCTION; INTESTINE MUCOSA; IRRITABLE COLON; LARGE INTESTINE; MICROFILAMENT; MICROFLORA; MICROTUBULE; NONHUMAN; PATHOPHYSIOLOGY; PERMEABILITY; PRIORITY JOURNAL; REVIEW; SMALL INTESTINE;

HUMANS; INTESTINAL DISEASES; INTESTINAL MUCOSA; INTESTINES; TIGHT JUNCTIONS;

EID: 84861170097     PISSN: 13501925     EISSN: 13652982     Source Type: Journal    
DOI: 10.1111/j.1365-2982.2012.01921.x     Document Type: Review

References (82)

1. Keita AV, Söderholm JD. The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil 2010; 22: 718-33.
2. Kim YS, Ho SB. Intestinal goblet cells and mucins in health and disease: recent insights and progress. Curr Gastroenterol Rep 2010; 12: 319-30.
3. Riley MA, Wertz JE. Bacteriocins: evolution, ecology, and application. Annu Rev Microbiol 2002; 56: 117-37.
4. Bevins CL, Salzmann NH. Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-68.
5. Atuma C, Strugala V, Allen A, Holm L. The adherent gastrointestinal mucus gel layer: thickness and physical state in vivo. Am J Physiol 2001; 280: G922-9.
6. Korjamo T, Heikkinen AT, Mönkkönen J. Analysis of unstirred water layer in vitro permeability experiments. J Pharm Sci 2009; 98: 4469-79.
7. Clayburgh DR, Shen L, Turner JR. A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest 2004; 84: 282-91.
8. Visser J, Rozing J, Sapone A, Lammers K, Fasano A. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann NY Acad Sci 2009; 1165: 95-205.
9. Hildalgo IJ, Raub TJ, Borchardt RT. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 1989; 96: 736-49.
10. Amasheh M, Andres S, Amasheh S, Fromm M, Schulzke JD. Barrier effects of nutritional factors. Ann NY Acad Sci 2009; 1165: 267-73.
11. Turner JR. Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 2009; 9: 799-809.
12. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 2011; 91: 151-75.
13. Veshnyakova A, Fromm M, Amasheh M, Amasheh S. Segmental expression of claudin proteins correlates with tight junction barrier properties in rat intestine. J Comp Physiol B 2010; 180: 591-8.
14. Arrieta MC, Bistritz L, Meddings JB. Alterations in intestinal permeability. Gut 2006; 55: 1512-20.
15. Piche T, Barbara G, Aubert P et al. Impaired intestinal barrier integrity in the colon of irritable bowel syndrome patients: involvement of soluble mediators. Gut 2009; 58: 196-201.
16. Lee JW, Park JH, Park DI et al. Subjects with diarrhea-predominant IBS have increased rectal permeability responsive to tryptase. Dig Dis Sci 2010; 55: 2922-8.
17. Zhou Q, Souba WW, Croce CM, Verne GN. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut 2010; 59: 775-84.
18. Van Itallie CM, Anderson JM. Measuring size-dependent permeability of the tight junction using PEG profiling. Methods Mol Biol 2011; 762: 1-11.
19. Yu AS. Electrophysiological characterization of claudin ion permeability using stably transfected epithelial cell lines. Methods Mol Biol 2011; 762: 27-41.
20. Shen L, Weber CR, Raleigh DR, Yu D, Turner JR. Tight junction pore and leak pathways: a dynamic duo. Ann Rev Physiol 2011; 73: 283-309.
21. Camilleri M, Gorman H. Intestinal permeability and irritable bowel syndrome. Neurogastroenterol Motil 2007; 19: 545-52.
22. Bjarnason I, MacPherson A, Hollander D. Intestinal permeability: an overview. Gastroenterology 1995; 108: 1566-81.
23. Meddings JB, Gibbons I. Discrimination of site-specific alterations in gastrointestinal permeability in the rat. Gastroenterology 1998; 114: 83-92.
24. Rao AS, Camilleri M, Eckert DJ et al. Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls. Am J Physiol 2011; 301: G919-28. Aug 11. doi:
25. Neunlist M, Toumi F, Oreschkova T et al. Human ENS regulates the intestinal epithelial barrier permeability and a tight junction-association protein Z)-1 via VIPergic pathways. Am J Physiol Gastrointestin Liver Physiol 2003; 285: G1028-36.
26. Jacob C, Yang PC, Darmoul D et al. Mast cell tryptase controls paracellular permeability of the intestine Role of protease-activated receptor 2 and beta-arrestins. J Biol Chem 2005; 280: 31936-48.
27. Bueno L, Fioramonti J. Protease-activated receptor 2 and gut permeability: a review. Neurogastroenterol Motil 2008; 20: 580-7.
28. Hollenberg MD. Proteinase-mediated signaling: proteinase-activated receptors (PARs) and much more. Life Sci 2003; 74: 237-46.
29. Goldblum SE, Rai U, Tripathi A et al. The active Zot domain (aa 288-293) increases ZO-1 and myosin 1C serine/threonine phosphorylation, alters interaction betnween ZO-1 and its binding partners, and induces tight junction disassembly through proteinase activated receptor 2 activation. FASEB J 2011; 25: 144-58.
30. Ewaschuk J, Diaz H, Meddings L et al. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am J Physiol 2008; 295: G1025-34.
31. Ukena S, Singh A, Dringenberg U et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. PLoS Biol 2007; 2: e1308.
32. Anderson RC, Cookson AL, McNabb WC et al. Lactobacillus plantarum MB452 enhances the function of the intestinal barrier by increasing the expression levels of genes involved in tight junction formation. BMC Microbiol 2010; 10: 316.
33. Fasano A, Fiorentini C, Donelli G et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest 1995; 96: 710-20.
34. Cario E, Gerken G, Podolsky DK. Toll-like receptor 2 controls mucosal inflammation by regulating epithelial barrier function. Gastroenterology 2007; 132: 1359-74.
35. Bansal T, Alaniz RC, Wood TK, Jayaraman A. The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci USA 2010; 107: 228-33.
36. Fukuda S, Toh H, Hase K et al. Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 2011; 469: 543-7.
37. Hamer HM, Jonkers D, Venema K et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 2008; 27: 104-19.
38. Pagnini C, Saeed R, Bamias G, Arseneau KO, Pizarro TT, Cominelli F. Probiotics promote gut health through stimulation of epithelial innate immunity. Proc Natl Acad Sci USA 2010; 107: 454-9.
39. Resta-Lenert SC, Barrett KE. Modulation of intestinal barrier properties by probiotics: role in reversing colitis. Ann NY Acad Sci 2009; 1165: 175-82.
40. Arrieta MC, Madsen K, Doyle J, Meddings J. Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut 2009; 58: 41-8.
41. Su L, Shen L, Clayburgh DR et al. Targeted epithelial tight junction dysfunction causes immune activation and contributes to development of experimental colitis. Gastroenterology 2009; 136: 551-63.
42. Watson AJ, Chu S, Sieck L et al. Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 2005; 129: 902-12.
43. Liu JJ RJ, Mah SJ, Thiesen AL et al. Epithelial gaps in a rodent model of inflammatory bowel disease: a quantitative validation study. Clin Transl Gastroenterol 2011; 2: e3.
44. Kiesslich R, Goetz M, Angus EM et al. Identification of epithelial gaps in human small and large intestine by confocal endomicroscopy. Gastroenterology 2007; 133: 1769-78.
45. Hanson PJ, Moran AP, Butler K. Paracellular permeability is increased by basal lipopolysaccharide in a primary culture of colonic epithelial cells; an effect prevented by an activator of Toll-like receptor-2. Innate Immun 2011; 17: 269-82.
46. Zuckerman MJ, Watts MT, Bhatt BD, Ho H. Intestinal permeability to [51Cr]EDTA in infectious diarrhea. Dig Dis Sci 1993; 38: 1651-7.
47. 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: 804-11.
48. Marshall JK, Thabane M, Garg AX et al. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther 2004; 20: 1317-22.
49. Villani AC, Lemire M, Thabane M et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 2010; 138: 1502-13.
50. Imielinski M, Baldassano RN, Griffiths A et al. Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet 2009; 41: 1335-40.
51. Spiller R, Swan C, Campbell E et al. Identifying and testing candidate genes underlying the inflammatory basis of irritable bowel syndrome. Gut 2011; 60: A164.
52. Zucchelli M, Camilleri M, Nixon AA et al. Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 2011; 41: 134-40.
53. Demaude J, Salvador-Cartier C, Fioramonti J et al. Phenotypic changes in colonocytes following acute stress or activation of mast cells in mice: implications for delayed epithelial barrier dysfunction. Gut 2006; 55: 655-61.
54. Dunlop SP, Hebden J, Campbell E et al. Abnormal intestinal permeability in subgroups of diarrhea-predominant irritable bowel syndromes. Am J Gastroenterol 2006; 101: 1288-94.
55. Park JH, Park DI, Kim HJ et al. The relationship between small-intestinal bacterial overgrowth and intestinal permeability in patients with irritable bowel syndrome. Gut 2009; 3: 174-9.
56. Liu Z, Qin H, Yang Z et al. Randomised clinical trial: the effects of perioperative probiotic treatment on barrier function and post-operative infectious complications in colorectal cancer surgery - a double-blind study. Aliment Pharmacol Ther 2011; 33: 50-63.
57. Zeng J, Li YQ, Zuo XL et al. Clinical trial: effect of active lactic acid bacteria on mucosal barrier function in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2008; 28: 994-1002.
58. Corinaldesi R, Stanghellini V, Cremon C et al. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof of concept study. Aliment Pharmacol Ther 2009; 30: 245-52.
59. Coeffier M, Gloro R, Boukhettala N et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 2010; 105: 1181-8.
60. Bertiaux-Vandaele N, Youmba SB, Belmonte L et al. The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol 2011; 106: 2165-73.
61. Visekruna A, Slavova N, Dullat S et al. Expression of catalytic proteasome subunits in the gut of patients with Crohn's disease. Int J Colorectal Dis 2009; 24: 1133-9.
62. Santos J, Saperas E, Nogueiras C et al. Release of mast cell mediators into the jejunum by cold pain stress in humans. Gastroenterology 1998; 114: 640-8.
63. Barbara G, Stanghellini V, De Giorgio R et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology 2004; 126: 693-702.
64. Piche T, Saint-Paul MC, Dainese R et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut 2008; 57: 468-73.
65. Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut 2004; 53: 1096-101.
66. Guilarte M, Santos J, deTorres I et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 2007; 56: 203-9.
67. Foley S, Garsed K, Singh G et al. Impaired uptake of serotonin by platelets from patients with irritable bowel syndrome correlates with duodenal immune activation. Gastroenterology 2011; 140: 1434-43.
68. Wallon C, Yang PC, Keita AV et al. Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut 2008; 57: 50-8.
69. Langhorst J, Junge A, Rueffer A et al. Elevated human beta-defensin-2 levels indicate an activation of the innate immune system in patients with irritable bowel syndrome. Am J Gastroenterol 2009; 104: 404-10.
70. Zhou Q, Zhang B, Verne GN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain 2009; 146: 41-6.
71. Klimberg VA, Souba WW. The importance of intestinal glutamine metabolism in maintaining a healthy gastrointestinal tract and supporting the body's response to injury and illness. Surg Annu 1990; 22: 61-76.
72. Labow BI, Souba WW. Glutamine. World J Surg 2000; 24: 1503-13.
73. Souba WW, Klimberg VS, Plumley DA et al. The role of glutamine in maintaning a healthy gut and supporting the metabolic response to injury and infection. J Surg Res 1990; 48: 383-91.
74. Yoshida S, Matsui M, Shirouzu Y et al. Effects of glutamine supplements and radiochemotherapy on the systemic immune and gut barrier function in patients with advanced esophageal cancer. Ann Surg 1998; 227: 485-91.
75. Sido B, Seel C, Hochlehnert A et al. Low intestinal glutamine level and low glutaminase activity in Crohn's Disease: a rational for glutamine supplementation? Dig Dis Sci 2006; 51: 2170-9.
76. DeMarco V, Dyess K, Strauss D et al. Inhibition of glutamine synthetase decreases proliferation of cultured rat intestinal epithelial cells. J Nutr 1999; 129: 57-62.
77. Kim J, Krichevsky A, Grad Y et al. Identification of many microRNAs that copurify with polyribomes in mammalian neurons. Proc Natl Acad Sci USA 2004; 101: 360-5.
78. Farh KK, Grimson A, Jan C et al. The widespread impact of mammalian microRNA on mRNA repression and evolution. Science 2005; 310: 1817-21.
79. Wu F, Zikusoka M, Trindade A, Dassopoulus T et al. MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2α. Gastroenterology 2008; 135: 1624-35.
80. Kapeller J, Houghton LA, Monnikes H et al. First evidence for an association of a functional variant in the microRNA-510 target site of the serotonin receptor-type 3E gene with diarrhea predominant irritable bowel syndrome. Hum Mol Genet 2008; 17: 2967-77.
81. Schulman RJ, Eakin MN, Czyzewski DJ et al. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008; 153: 646-50.
82. Chen HQ, Yang J, Zhang M et al. Lactobacillus plantarum ameliorates colonic epithelial barrier dysfunction by modulating the apical junctional complex and PepT1 in IL-10 knockout mice. Am J Physiol Gastrointest Liver Physiol 2010; 299: G1287-97.