Abstract
There is increasing concern in identifying the mechanisms underlying the intimate control of the intestinal barrier, as deregulation of its function is strongly associated with digestive (organic and functional) and a number of non-digestive (schizophrenia, diabetes, sepsis, among others) disorders. The intestinal barrier is a complex and effective defensive functional system that operates to limit luminal antigen access to the internal milieu while maintaining nutrient and electrolyte absorption. Intestinal permeability to substances is mainly determined by the physicochemical properties of the barrier, with the epithelium, mucosal immunity, and neural activity playing a major role. In functional gastrointestinal disorders (FGIDs), the absence of structural or biochemical abnormalities that explain chronic symptoms is probably close to its end, as recent research is providing evidence of structural gut alterations, at least in certain subsets, mainly in functional dyspepsia (FD) and irritable bowel syndrome (IBS). These alterations are associated with increased permeability, which seems to reflect mucosal inflammation and neural activation. The participation of each anatomical and functional component of barrier function in homeostasis and intestinal dysfunction is described, with a special focus on FGIDs.
Keywords
All authors contributed equally to the preparation and edition of the manuscript.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Ait-Belgnaoui A, Bradesi S, Fioramonti J, Theodorou V, Bueno L (2005) Acute stress-induced hypersensitivity to colonic distension depends upon increase in paracellular permeability: role of myosin light chain kinase. Pain 113:141–147
Al-Sadi R, Ye D, Dokladny K, Ma TY (2008) Mechanism of IL-1beta-induced increase in intestinal epithelial tight junction permeability. J Immunol 180:5653–5661
Arrieta MC, Madsen K, Doyle J, Meddings J (2009) Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut 58:41–48
Avila EE (2016) Functions of antimicrobial peptides in vertebrates. Curr Protein Pept Sci (Epub ahead of print)
Aziz Q, Fass R, Gyawali CP, Miwa H, Pandolfino JE, Zerbib F (2016) Functional esophageal disorders. Gastroenterology 150(6):1368–1379
Barreau F, Cartier C, Leveque M, Ferrier L, Moriez R, Laroute V, Rosztoczy A, Fioramonti J, Bueno L (2007) Pathways involved in gut mucosal barrier dysfunction induced in adult rats by maternal deprivation: corticotrophin-releasing factor and nerve growth factor interplay. J Physiol 580:347–356
Basra S, Verne GN, Zhou QQ (2013) Randomized placebo-controlled trial of glutamine for the treatment of diarrhea-predominant IBS. Gastroenterology 144:S160–S160
Basu R, O’Quinn DB, Silberger DJ, Schoeb TR, Fouser L, Ouyang W, Hatton RD, Weaver CT (2012) Th22 cells are an important source of IL-22 for host protection against enteropathogenic bacteria. Immunity 37:1061–1075
Beutheu S, Ghouzali I, Galas L, Dechelotte P, Coeffier M (2013) Glutamine and arginine improve permeability and tight junction protein expression in methotrexate-treated Caco-2 cells. Clin Nutr 32:863–869
Bevins CL, Salzman NH (2011) Paneth cells, antimicrobial peptides and maintenance of intestinal homeostasis. Nat Rev Microbiol 9:356–368
Bischoff SC, Barbara G, Buurman W, Ockhuizen T, Schulzke JD, Serino M, Tilg H, Watson A, Wells JM (2014) Intestinal permeability – a new target for disease prevention and therapy. BMC Gastroenterol 14:189
Bono MR, Tejon G, Flores-Santibanez F, Fernandez D, Rosemblatt M, Sauma D (2016) Retinoic acid as a modulator of T cell immunity. Nutrients 8:349
Brandtzaeg P, Kiyono H, Pabst R, Russell MW (2008) Terminology: nomenclature of mucosa-associated lymphoid tissue. Mucosal Immunol 1:31–37
Brierley SM, Linden DR (2014) Neuroplasticity and dysfunction after gastrointestinal inflammation. Nat Rev Gastroenterol Hepatol 11:611–627
Bye WA, Allan CH, Trier JS (1984) Structure, distribution, and origin of M cells in Peyer’s patches of mouse ileum. Gastroenterology 86:789–801
Camilleri M, Lasch K, Zhou W (2012) Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 303:G775–G785
Castillo EJ, Camilleri M, Locke GR, Burton DD, Stephens DA, Geno DM, Zinsmeister AR (2004) A community-based, controlled study of the epidemiology and pathophysiology of dyspepsia. Clin Gastroenterol Hepatol 2:985–996
Cerutti A (2008) The regulation of IgA class switching. Nat Rev Immunol 8:421–434
Cheroutre H, Lambolez F, Mucida D (2011) The light and dark sides of intestinal intraepithelial lymphocytes. Nat Rev Immunol 11:445–456
Clark EC, Patel SD, Chadwick PR, Warhurst G, Curry A, Carlson GL (2003) Glutamine deprivation facilitates tumour necrosis factor induced bacterial translocation in Caco-2 cells by depletion of enterocyte fuel substrate. Gut 52:224–230
Coeffier M, Gloro R, Boukhettala N, Aziz M, Lecleire S, Vandaele N, Antonietti M, Savoye G, Bole-Feysot C, Dechelotte P, Reimund JM, Ducrotte P (2010) Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol 105:1181–1188
Coombes JL, Powrie F (2008) Dendritic cells in intestinal immune regulation. Nat Rev Immunol 8:435–446
Corinaldesi R, Stanghellini V, Cremon C, Gargano L, Cogliandro RF, De Giorgio R, Bartesaghi G, Canovi B, Barbara G (2009) Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study. Aliment Pharmacol Ther 30:245–252
De Palma G, Collins SM, Bercik P, Verdu EF (2014) The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J Physiol 592:2989–2997
Den Hond E, Hiele M, Peeters M, Ghoos Y, Rutgeerts P (1999) Effect of long-term oral glutamine supplements on small intestinal permeability in patients with Crohn’s disease. JPEN J Parenter Enteral Nutr 23:7–11
Drossman DA (2016) Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology 150(6):1262–1279
Farquhar MG, Palade GE (1963) Junctional complexes in various epithelia. J Cell Biol 17:375–412
Farre R, Auli M, Lecea B, Martinez E, Clave P (2006) Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. J Pharmacol Exp Ther 316:1238–1248
Farre R, Vanheel H, Vanuytsel T, Masaoka T, Tornblom H, Simren M, Van Oudenhove L, Tack JF (2013) In functional dyspepsia, hypersensitivity to postprandial distention correlates with meal-related symptom severity. Gastroenterology 145:566–573
Fasano A (2011) Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev 91:151–175
Feighery LM, Cochrane SW, Quinn T, Baird AW, O’Toole D, Owens SE, O’Donoghue D, Mrsny RJ, Brayden DJ (2008) Myosin light chain kinase inhibition: correction of increased intestinal epithelial permeability in vitro. Pharm Res 25:1377–1386
Fichna J, Salaga M, Stuart J, Saur D, Sobczak M, Zatorski H, Timmermans JP, Bradshaw HB, Ahn K, Storr MA (2014) Selective inhibition of FAAH produces antidiarrheal and antinociceptive effect mediated by endocannabinoids and cannabinoid-like fatty acid amides. Neurogastroenterol Motil 26:470–481
Friesen CA, Sandridge L, Andre L, Roberts CC, Abdel-Rahman SM (2006) Mucosal eosinophilia and response to H1/H2 antagonist and cromolyn therapy in pediatric dyspepsia. Clin Pediatr (Phila) 45:143–147
Fukata M, Arditi M (2013) The role of pattern recognition receptors in intestinal inflammation. Mucosal Immunol 6:451–463
Fukuda S, Toh H, Hase K, Oshima K, Nakanishi Y, Yoshimura K, Tobe T, Clarke JM, Topping DL, Suzuki T, Taylor TD, Itoh K, Kikuchi J, Morita H, Hattori M, Ohno H (2011) Bifidobacteria can protect from enteropathogenic infection through production of acetate. Nature 469:543–547
Furness JB, Kunze WA, Bertrand PP, Clerc N, Bornstein JC (1998) Intrinsic primary afferent neurons of the intestine. Prog Neurobiol 54:1–18
Gallego D, Gil V, Aleu J, Auli M, Clave P, Jimenez M (2008) Purinergic and nitrergic junction potential in the human colon. Am J Physiol Gastrointest Liver Physiol 295:G522–G533
Gerlach K, McKenzie AN, Neurath MF, Weigmann B (2015) IL-9 regulates intestinal barrier function in experimental T cell-mediated colitis. Tissue Barriers 3:e983777
Goke M, Kanai M, Podolsky DK (1998) Intestinal fibroblasts regulate intestinal epithelial cell proliferation via hepatocyte growth factor. Am J Physiol 274:G809–G818
Gopalakrishnan S, Durai M, Kitchens K, Tamiz AP, Somerville R, Ginski M, Paterson BM, Murray JA, Verdu EF, Alkan SS, Pandey NB (2012) Larazotide acetate regulates epithelial tight junctions in vitro and in vivo. Peptides 35:86–94
Gunzel D, Yu AS (2013) Claudins and the modulation of tight junction permeability. Physiol Rev 93:525–569
Guttman JA, Finlay BB (2009) Tight junctions as targets of infectious agents. Biochim Biophys Acta 1788:832–841
Hammer AM, Morris NL, Earley ZM, Choudhry MA (2015) The first line of defense: the effects of alcohol on post-burn intestinal barrier, immune cells, and microbiome. Alcohol Res 37:209–222
Han B, Sheng B, Zhang Z, Pu A, Yin J, Wang Q, Yang K, Sun L, Yu M, Qiu Y, Xiao W, Yang H (2016) Aryl hydrocarbon receptor activation in intestinal obstruction ameliorates intestinal barrier dysfunction via suppression of MLCK-MLC phosphorylation pathway. Shock 46(3):319–328
Hartsock A, Nelson WJ (2008) Adherens and tight junctions: structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778:660–669
Hooper LV, Macpherson AJ (2010) Immune adaptations that maintain homeostasis with the intestinal microbiota. Nat Rev Immunol 10:159–169
Jovov B, Que J, Tobey NA, Djukic Z, Hogan BL, Orlando RC (2011) Role of E-cadherin in the pathogenesis of gastroesophageal reflux disease. Am J Gastroenterol 106:1039–1047
Kale G, Naren AP, Sheth P, Rao RK (2003) Tyrosine phosphorylation of occludin attenuates its interactions with ZO-1, ZO-2, and ZO-3. Biochem Biophys Res Commun 302:324–329
Keita AV, Soderholm JD (2010) The intestinal barrier and its regulation by neuroimmune factors. Neurogastroenterol Motil 22:718–733
Keita AV, Salim SY, Jiang T, Yang PC, Franzen L, Soderkvist P, Magnusson KE, Soderholm JD (2008) Increased uptake of non-pathogenic E. coli via the follicle-associated epithelium in longstanding ileal Crohn’s disease. J Pathol 215:135–144
Kelly CP, Green PH, Murray JA, Dimarino A, Colatrella A, Leffler DA, Alexander T, Arsenescu R, Leon F, Jiang JG, Arterburn LA, Paterson BM, Fedorak RN, Larazotide Acetate Celiac Disease Study G (2013) Larazotide acetate in patients with coeliac disease undergoing a gluten challenge: a randomised placebo-controlled study. Aliment Pharmacol Ther 37:252–262
Kelly JR, Kennedy PJ, Cryan JF, Dinan TG, Clarke G, Hyland NP (2015) Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. Front Cell Neurosci 9:392
Kim M, Ashida H, Ogawa M, Yoshikawa Y, Mimuro H, Sasakawa C (2010) Bacterial interactions with the host epithelium. Cell Host Microbe 8:20–35
Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE (2010) The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut 59:1213–1221
Koch S, Nusrat A (2009) Dynamic regulation of epithelial cell fate and barrier function by intercellular junctions. Ann N Y Acad Sci 1165:220–227
Kouznetsova L, Bijlsma PB, van Leeuwen PA, Groot JA, Houdijk AP (1999) Glutamine reduces phorbol-12,13-dibutyrate-induced macromolecular hyperpermeability in HT-29Cl.19A intestinal cells. JPEN J Parenter Enteral Nutr 23:136–139
Krug SM, Amasheh S, Richter JF, Milatz S, Gunzel D, Westphal JK, Huber O, Schulzke JD, Fromm M (2009a) Tricellulin forms a barrier to macromolecules in tricellular tight junctions without affecting ion permeability. Mol Biol Cell 20:3713–3724
Krug SM, Fromm M, Gunzel D (2009b) Two-path impedance spectroscopy for measuring paracellular and transcellular epithelial resistance. Biophys J 97:2202–2211
Le Bacquer O, Laboisse C, Darmaun D (2003) Glutamine preserves protein synthesis and paracellular permeability in Caco-2 cells submitted to “luminal fasting”. Am J Physiol Gastrointest Liver Physiol 285:G128–G136
Leffler DA, Kelly CP, Abdallah HZ, Colatrella AM, Harris LA, Leon F, Arterburn LA, Paterson BM, Lan ZH, Murray JA (2012) A randomized, double-blind study of larazotide acetate to prevent the activation of celiac disease during gluten challenge. Am J Gastroenterol 107:1554–1562
Leffler DA, Kelly CP, Green PH, Fedorak RN, DiMarino A, Perrow W, Rasmussen H, Wang C, Bercik P, Bachir NM, Murray JA (2015) Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. Gastroenterology 148:1311–1319 e1316
Lindemann B (2001) Hans Ussing, experiments and models. J Membr Biol 184:203–210
Lindner C, Thomsen I, Wahl B, Ugur M, Sethi MK, Friedrichsen M, Smoczek A, Ott S, Baumann U, Suerbaum S, Schreiber S, Bleich A, Gaboriau-Routhiau V, Cerf-Bensussan N, Hazanov H, Mehr R, Boysen P, Rosenstiel P, Pabst O (2015) Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Nat Immunol 16:880–888
Lobo B, Pigrau M, Martinez C, Gonzalez-Castro AM, Guilarte M, de Torres I, Salvo-Romero E, Rodino-Janeiro BK, Fortea M, Cotoner CA, Azpiroz F, Vicario M, Santos J (2015) Clinical benefit and intestinal mucosal transcriptome modulation after long-term mast cell stabilization with oral disodium cromoglycate in diarrhea-predominant irritable bowel syndrome (IBS-D) patients. Gastroenterology 148:S494–S494
Lovell RM, Ford AC (2012) Global prevalence of and risk factors for irritable bowel syndrome: a meta-analysis. Clin Gastroenterol Hepatol 10:712–721.e714
Martin TA, Jiang WG (2009) Loss of tight junction barrier function and its role in cancer metastasis. Biochim Biophys Acta 1788:872–891
Martinez C, Vicario M, Ramos L, Lobo B, Mosquera JL, Alonso C, Sanchez A, Guilarte M, Antolin M, de Torres I, Gonzalez-Castro AM, Pigrau M, Saperas E, Azpiroz F, Santos J (2012) The jejunum of diarrhea-predominant irritable bowel syndrome shows molecular alterations in the tight junction signaling pathway that are associated with mucosal pathobiology and clinical manifestations. Am J Gastroenterol 107:736–746
Martinez C, Lobo B, Pigrau M, Ramos L, Gonzalez-Castro AM, Alonso C, Guilarte M, Guila M, de Torres I, Azpiroz F, Santos J, Vicario M (2013) Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut 62:1160–1168
Mereu A, Tedo G, Moeser AJ, Rimbach G, Ipharraguerre IR (2015) Cromolyn-mediated improvement of intestinal barrier function is associated with enhanced piglet performance after weaning. BMC Vet Res 11:274
Million M, Zhao JF, Luckey A, Czimmer J, Maynard GD, Kehne J, Hoffman DC, Tache Y (2013) The newly developed CRF1-receptor antagonists, NGD 98-2 and NGD 9002, suppress acute stress-induced stimulation of colonic motor function and visceral hypersensitivity in rats. PLoS One 8:e73749
Monkemuller K, Wex T, Kuester D, Fry LC, Kandulski A, Kropf S, Roessner A, Malfertheiner P (2012) Role of tight junction proteins in gastroesophageal reflux disease. BMC Gastroenterol 12:128
Moriez R, Salvador-Cartier C, Theodorou V, Fioramonti J, Eutamene H, Bueno L (2005) Myosin light chain kinase is involved in lipopolysaccharide-induced disruption of colonic epithelial barrier and bacterial translocation in rats. Am J Pathol 167:1071–1079
Morris G, Berk M, Carvalho A, Caso JR, Sanz Y, Walder K, Maes M (2016) The role of the microbial metabolites including tryptophan catabolites and short chain fatty acids in the patho-physiology of immune-inflammatory and neuroimmune disease. Mol Neurobiol. doi:10.1007/s12035-016-0004-2 (Epub ahead of print)
Neish AS (2009) Microbes in gastrointestinal health and disease. Gastroenterology 136:65–80
Noyer CM, Simon D, Borczuk A, Brandt LJ, Lee MJ, Nehra V (1998) A double-blind placebo-controlled pilot study of glutamine therapy for abnormal intestinal permeability in patients with AIDS. Am J Gastroenterol 93:972–975
Opazo A, Lecea B, Gil V, Jimenez M, Clave P, Gallego D (2011) Specific and complementary roles for nitric oxide and ATP in the inhibitory motor pathways to rat internal anal sphincter. Neurogastroenterol Motil 23:e11–e25
O’Shea JJ, Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4+ T cells. Science 327:1098–1102
Park MY, Kim MY, Seo YR, Kim JS, Sung MK (2016) High-fat diet accelerates intestinal tumorigenesis through disrupting intestinal cell membrane integrity. J Cancer Prev 21:95–103
Pascual S, Martinez J, Perez-Mateo M (2001) The intestinal barrier: functional disorders in digestive and non-digestive diseases. Gastroenterol Hepatol 24:256–267
Peng X, Yan H, You Z, Wang P, Wang S (2004) Effects of enteral supplementation with glutamine granules on intestinal mucosal barrier function in severe burned patients. Burns 30:135–139
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 (2009) Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 58:196–201
Rodino-Janeiro BK, Alonso-Cotoner C, Pigrau M, Lobo B, Vicario M, Santos J (2015) Role of corticotropin-releasing factor in gastrointestinal permeability. J Neurogastroenterol Motil 21:33–50
Saitou M, Fujimoto K, Doi Y, Itoh M, Fujimoto T, Furuse M, Takano H, Noda T, Tsukita S (1998) Occludin-deficient embryonic stem cells can differentiate into polarized epithelial cells bearing tight junctions. J Cell Biol 141:397–408
Santaolalla R, Abreu MT (2012) Innate immunity in the small intestine. Curr Opin Gastroenterol 28:124–129
Schwarz BT, Wang F, Shen L, Clayburgh DR, Su L, Wang Y, Fu YX, Turner JR (2007) LIGHT signals directly to intestinal epithelia to cause barrier dysfunction via cytoskeletal and endocytic mechanisms. Gastroenterology 132:2383–2394
Sergent T, Piront N, Meurice J, Toussaint O, Schneider YJ (2010) Anti-inflammatory effects of dietary phenolic compounds in an in vitro model of inflamed human intestinal epithelium. Chem Biol Interact 188:659–667
Severson EA, Lee WY, Capaldo CT, Nusrat A, Parkos CA (2009) Junctional adhesion molecule A interacts with Afadin and PDZ-GEF2 to activate Rap1A, regulate beta1 integrin levels, and enhance cell migration. Mol Biol Cell 20:1916–1925
Shan M, Gentile M, Yeiser JR, Walland AC, Bornstein VU, Chen K, He B, Cassis L, Bigas A, Cols M, Comerma L, Huang B, Blander JM, Xiong H, Mayer L, Berin C, Augenlicht LH, Velcich A, Cerutti A (2013) Mucus enhances gut homeostasis and oral tolerance by delivering immunoregulatory signals. Science 342:447–453
Shen L, Turner JR (2006) Role of epithelial cells in initiation and propagation of intestinal inflammation. Eliminating the static: tight junction dynamics exposed. Am J Physiol Gastrointest Liver Physiol 290:G577–G582
Singh P, Agnihotri A, Pathak MK, Shirazi A, Tiwari RP, Sreenivas V, Sagar R, Makharia GK (2012) Psychiatric, somatic and other functional gastrointestinal disorders in patients with irritable bowel syndrome at a tertiary care center. J Neurogastroenterol Motil 18:324–331
Sternberg EM (2006) Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens. Nat Rev Immunol 6:318–328
Suzuki T, Hara H (2009) Quercetin enhances intestinal barrier function through the assembly of zonula [corrected] occludens-2, occludin, and claudin-1 and the expression of claudin-4 in Caco-2 cells. J Nutr 139:965–974
Tanaka H, Takechi M, Kiyonari H, Shioi G, Tamura A, Tsukita S (2015) Intestinal deletion of Claudin-7 enhances paracellular organic solute flux and initiates colonic inflammation in mice. Gut 64:1529–1538
Tonini M, De Giorgio R, De Ponti F, Sternini C, Spelta V, Dionigi P, Barbara G, Stanghellini V, Corinaldesi R (2000) Role of nitric oxide- and vasoactive intestinal polypeptide-containing neurones in human gastric fundus strip relaxations. Br J Pharmacol 129:12–20
Turner JR (2009) Intestinal mucosal barrier function in health and disease. Nat Rev Immunol 9:799–809
Vakil N, van Zanten SV, Kahrilas P, Dent J, Jones R, Global Consensus G (2006) The Montreal definition and classification of gastroesophageal reflux disease: a global evidence-based consensus. Am J Gastroenterol 101:1900–1920 (quiz 1943)
van der Flier LG, Clevers H (2009) Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu Rev Physiol 71:241–260
Vanheel H, Farre R (2013) Changes in gastrointestinal tract function and structure in functional dyspepsia. Nat Rev Gastroenterol Hepatol 10:142–149
Vanheel H, Vicario M, Vanuytsel T, Van Oudenhove L, Martinez C, Keita AV, Pardon N, Santos J, Soderholm JD, Tack J, Farre R (2014) Impaired duodenal mucosal integrity and low-grade inflammation in functional dyspepsia. Gut 63:262–271
Vanheel H, Vicario M, Vanuytsel T, Tack JF, Farre R (2015) Eosinophils and mast cells in functional dyspepsia: ultrastructural evaluation of activation. Gastroenterology 148:S49
Vanuytsel T, van Wanrooy S, Vanheel H, Vanormelingen C, Verschueren S, Houben E, Salim Rasoel S, Tomicronth J, Holvoet L, Farre R, Van Oudenhove L, Boeckxstaens G, Verbeke K, Tack J (2014a) Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism. Gut 63:1293–1299
Vanuytsel T, Vanormelingen C, Vanheel H, Masaoka T, Salim Rasoel S, Toth J, Houben E, Verbeke K, De Hertogh G, Vanden Berghe P, Tack J, Farre R (2014b) From intestinal permeability to dysmotility: the biobreeding rat as a model for functional gastrointestinal disorders. PLoS One 9:e111132
Vicario M, Gonzalez-Castro AM, Martinez C, Lobo B, Pigrau M, Guilarte M, de Torres I, Mosquera JL, Fortea M, Sevillano-Aguilera C, Salvo-Romero E, Alonso C, Rodino-Janeiro BK, Soderholm JD, Azpiroz F, Santos J (2015) Increased humoral immunity in the jejunum of diarrhoea-predominant irritable bowel syndrome associated with clinical manifestations. Gut 64:1379–1388
Wallon C, Yang PC, Keita AV, Ericson AC, McKay DM, Sherman PM, Perdue MH, Soderholm JD (2008) Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut 57:50–58
Wang B, Wu Z, Ji Y, Sun K, Dai Z, Wu G (2016) L-glutamine enhances tight junction integrity by activating CaMK kinase 2-AMP-activated protein kinase signaling in intestinal porcine epithelial cells. J Nutr 146:501–508
Watson CJ, Hoare CJ, Garrod DR, Carlson GL, Warhurst G (2005) Interferon-gamma selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores. J Cell Sci 118:5221–5230
Weber CR, Raleigh DR, Su L, Shen L, Sullivan EA, Wang Y, Turner JR (2010) Epithelial myosin light chain kinase activation induces mucosal interleukin-13 expression to alter tight junction ion selectivity. J Biol Chem 285:12037–12046
Wex T, Monkemuller K, Stahr A, Kuester D, Fry LC, Volkel S, Kandulski A, Roessner A, Malfertheiner P (2012) Gastro-oesophageal reflux disease is associated with up-regulation of desmosomal components in oesophageal mucosa. Histopathology 60:405–415
Wu LL, Peng WH, Kuo WT, Huang CY, Ni YH, Lu KS, Turner JR, Yu LC (2014) Commensal bacterial endocytosis in epithelial cells is dependent on myosin light chain kinase-activated brush border fanning by interferon-gamma. Am J Pathol 184:2260–2274
Zeissig S, Burgel N, Gunzel D, Richter J, Mankertz J, Wahnschaffe U, Kroesen AJ, Zeitz M, Fromm M, Schulzke JD (2007) 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 56:61–72
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Appendices
Funding
Supported in part by Fondo Europeo de Desarrollo Regional (FEDER), Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Subdirección General de Investigación Sanitaria, Ministerio de Economía y Competitividad: CP10/00502 and PI13/00935 (MV), and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (RF, MV).
Conflict of Interest
The authors disclose no conflicts of interest and no financial arrangements with any company whose product figures in the submitted manuscript.
Rights and permissions
Copyright information
© 2016 Springer International Publishing AG
About this chapter
Cite this chapter
Farré, R., Vicario, M. (2016). Abnormal Barrier Function in Gastrointestinal Disorders. In: Greenwood-Van Meerveld, B. (eds) Gastrointestinal Pharmacology . Handbook of Experimental Pharmacology, vol 239. Springer, Cham. https://doi.org/10.1007/164_2016_107
Download citation
DOI: https://doi.org/10.1007/164_2016_107
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-56359-6
Online ISBN: 978-3-319-56360-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)