Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier
Abstract
Objective: Recently, the authors demonstrated altered gene expression in the jejunal mucosa of diarrhoea-predominant irritable bowel syndrome patients (IBS-D); specifically, the authors showed that genes related to mast cells and the intercellular apical junction complex (AJC) were expressed differently than in healthy subjects. The aim of the authors here was to determine whether these alterations are associated with structural abnormalities in AJC and their relationship with mast cell activation and IBS-D clinical manifestations. Design: A clinical assessment and a jejunal biopsy were obtained in IBS-D patients (n=45) and healthy subjects (n=30). Mucosal mast cell number and activation were determined by quantifying CD117 + cells/hpf and tryptase expression, respectively. Expression and distribution of AJC specific proteins were evaluated by western blot and confocal microscopy. AJC ultrastructure was assessed by transmission electron microscopy. Results: Compared with healthy subjects, IBS-D patients exhibited: (a) increased mast cell counts and activation; (b) increased protein expression of claudin-2, reduced occludin phosphorylation and enhanced redistribution from the membrane to the cytoplasm; and (c) increased myosin kinase expression, reduced myosin phosphatase and, consequently, enhanced phosphorylation of myosin. These molecular alterations were associated with ultrastructural abnormalities at the AJC, specifically, perijunctional cytoskeleton condensation and enlarged apical intercellular distance. Moreover, AJC structural alterations positively correlated both with mast cell activation and clinical symptoms. Conclusion: The jejunal mucosa of IBS-D patients displays disrupted apical junctional complex integrity associated with mast cell activation and clinical manifestations. These results provide evidence for the organic nature of IBS-D, a heretofore model disease of functional gastrointestinal disorders.
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The alteration of intestinal barrier function, with increased gut permeability, has a major role in IBS; nevertheless, its relationship with altered microbiota remains to be fully understood.
“The alteration of intestinal barrier function, with increased gut permeability, has a major role in IBS [64] ; nevertheless, its relationship with altered microbiota remains to be fully understood.”
From Intestinal microbiota in health and disease: Role of bifidobacteria in gut homeostasis (2014) · cites this paper as [64]
Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
The social readjustment rating scale
Holmes, T. H., & Rahe, R. H. (1967) · Journal of Psychosomatic Research · doi:10.1016/0022-3999(67)90010-4 · Cited by 11,174 · see citing works
Intestinal mucosal barrier function in health and disease
Turner, J. R. (2009) · Nature reviews. Immunology · doi:10.1038/nri2653 · Cited by 3,952 · see citing works
Stool form scale as a useful guide to intestinal transit time
Lewis, S. J., & Heaton, K. W. (1997) · Scandinavian Journal of Gastroenterology · doi:10.3109/00365529709011203 · Cited by 3,244 · see citing works
Functional Gastroduodenal Disorders
Tack, J., Talley, N. J., Camilleri, M., Holtmann, G., Hu, P., Malagelada, J.-R., & Stanghellini, V. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.059 · Cited by 2,418 · see citing works
Barbara, G., Stanghellini, V., De Giorgio, R., Cremon, C., Cottrell, G. S., Santini, D., Pasquinelli, G., Morselli-Labate, A. M., Grady, E. F., Bunnett, N. W., et al. (2004) · Gastroenterology · doi:10.1053/j.gastro.2003.11.055 · Cited by 1,475 · see citing works
CLAUDINS AND EPITHELIAL PARACELLULAR TRANSPORT
Itallie, C. M. V., & Anderson, J. M. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.68.040104.131404 · Cited by 1,123 · see citing works
Activation of the mucosal immune system in irritable bowel syndrome
Chadwick, V. S., Chen, W., Shu, D., Paulus, B., Bethwaite, P., Tie, A., & Wilson, I. (2002) · Gastroenterology · doi:10.1053/gast.2002.33579 · Cited by 833 · see citing works
Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells
Amasheh, S., Meiri, N., Gitter, A. H., Schöneberg, T., Mankertz, J., Schulzke, J. D., & Fromm, M. (2002) · Journal of Cell Science · doi:10.1242/jcs.00165 · Cited by 812 · see citing works
Functional gastroduodenal disorders
Talley, N. J., Stanghellini, V., Heading, R. C., Koch, K. L., Malagelada, J., & Tytgat, G. N. J. (1999) · Gut · doi:10.1136/gut.45.2008.ii37 · Cited by 797 · see citing works
Mast Cell-Dependent Excitation of Visceral-Nociceptive Sensory Neurons in Irritable Bowel Syndrome
Barbara, G., Wang, B., Stanghellini, V., de Giorgio, R., Cremon, C., Di Nardo, G., Trevisani, M., Campi, B., Geppetti, P., Tonini, M., et al. (2007) · Gastroenterology · doi:10.1053/j.gastro.2006.11.039 · Cited by 783 · see citing works
Dinan, T. G., Quigley, E. M. M., Ahmed, S. M. M., Scully, P., O’Brien, S., O’Mahony, L., O’Mahony, S., Shanahan, F., & Keeling, P. W. N. (2006) · Gastroenterology · doi:10.1053/j.gastro.2005.11.033 · Cited by 636 · see citing works
Possible Involvement of Phosphorylation of Occludin in Tight Junction Formation
Sakakibara, A., Furuse, M., Saitou, M., Ando‐Akatsuka, Y., & Tsukita, S. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.137.6.1393 · Cited by 590 · see citing works
Piche, T., Barbara, G., Aubert, P., Bruley des Varannes, S., Dainese, R., Nano, J. L., Cremon, C., Stanghellini, V, De Giorgio, R., Galmiche, J. P., et al. (2009) · Gut · doi:10.1136/gut.2007.140806 · Cited by 540 · see citing works
Abnormal Intestinal Permeability in Subgroups of Diarrhea-Predominant Irritable Bowel Syndromes
Dunlop, S. P., Hebden, J., Campbell, E., Naesdal, J., Olbe, L., Perkins, A. C., & Spiller, R. C. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00672.x · Cited by 476 · see citing works
Marchiando, A. M., Shen, L., Graham, W. V., Weber, C. R., Schwarz, B. T., Austin, J. R., Raleigh, D. R., Guan, Y., Watson, A. J. M., Montrose, M. H., et al. (2010) · The Journal of Cell Biology · doi:10.1083/jcb.200902153 · Cited by 475 · see citing works
Clayburgh, D. R. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24970 · Cited by 419 · see citing works
Gwee, K.-A. (2003) · Gut · doi:10.1136/gut.52.4.523 · Cited by 415 · see citing works
Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum
Guilarte, M., Santos, J., de Torres, I., Alonso, C., Vicario, M., Ramos, L., Martinez, C., Casellas, F., Saperas, E., & Malagelada, J. R. (2007) · Gut · doi:10.1136/gut.2006.100594 · Cited by 385 · see citing works
Self-citationIntestinal membrane permeability and hypersensitivity in the irritable bowel syndrome
Zhou, Q., Zhang, B., & Verne, N. G. (2009) · Pain · doi:10.1016/j.pain.2009.06.017 · Cited by 373 · see citing works
Mast Cell Tryptase Controls Paracellular Permeability of the Intestine
Jacob, C., Yang, P.-C., Darmoul, D., Amadesi, S., Saito, T., Cottrell, G. S., Coelho, A.-M., Singh, P., Grady, E. F., Perdue, M., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506338200 · Cited by 334 · see citing works
Gecse, K., Róka, R., Ferrier, L., Leveque, M., Eutamene, H., Cartier, C., Ait-Belgnaoui, A., Rosztóczy, A., Izbéki, F., Fioramonti, J., et al. (2008) · Gut · doi:10.1136/gut.2007.140210 · Cited by 314 · see citing works
Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat
Santos, J., Yang, P.-C., Söderholm, J. D., Benjamin, M., & Perdue, M. H. (2001) · Gut · doi:10.1136/gut.48.5.630 · Cited by 313 · see citing works
Self-citationBertiaux-Vandaële, N., Beutheu, S., Belmonte, L., Lecleire, S., Antonietti, M., Gourcerol, G., Leroi, A., Déchelotte, P., Ménard, J.-F., Ducrotte, P. R., et al. (2011) · The American Journal of Gastroenterology · doi:10.1038/ajg.2011.257 · Cited by 296 · see citing works
Söderholm, J. D., Olaison, G., Peterson, K. H., Franzén, L. E., Lindmark, T., Wirén, M., Tagesson, C., & Sjödahl, R. (2002) · Gut · doi:10.1136/gut.50.3.307 · Cited by 290 · see citing works
WALKER, M. M., TALLEY, N. J., PRABHAKAR, M., PENNANEAC’H, C. J., ARO, P., RONKAINEN, J., STORSKRUBB, T., HARMSEN, W. S., ZINSMEISTER, A. R., & AGREUS, L. (2009) · Alimentary Pharmacology & Therapeutics · doi:10.1111/j.1365-2036.2009.03937.x · Cited by 261 · see citing works
Simonović, I., Rosenberg, J. S., Koutsouris, A., & Hecht, G. A. (2000) · Cellular Microbiology · doi:10.1046/j.1462-5822.2000.00055.x · Cited by 256 · see citing works
Corticotropin-releasing hormone mimics stress-induced colonic epithelial pathophysiology in the rat
Santos, J., Saunders, P. R., Hanssen, N. P. M., Yang, P., Yates, D. A., Groot, J. A., & Perdue, M. H. (1999) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.1999.277.2.g391 · Cited by 251 · see citing works
Self-citationBalda, M. S., & Matter, K. (2008) · Journal of Cell Science · doi:10.1242/jcs.023887 · Cited by 235 · see citing works
Occludin Phosphorylation in Regulation of Epithelial Tight Junctions
Rao, R. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04054.x · Cited by 230 · see citing works
Martínez, C., Vicario, M., Ramos, L., Lobo, B., Mosquera, J. L., Alonso, C., Sánchez, A., Guilarte, M., Antolín, M., de Torres, I., et al. (2012) · American Journal of Gastroenterology · doi:10.1038/ajg.2011.472 · Cited by 214 · see citing works
Self-citationIncreased Proteasome-Mediated Degradation of Occludin in Irritable Bowel Syndrome
Coëffier, M., Gloro, R., Boukhettala, N., Aziz, M., Lecleire, S., Vandaele, N., Antonietti, M., Savoye, G., Bôle-Feysot, C., Déchelotte, P., et al. (2010) · American Journal of Gastroenterology · doi:10.1038/ajg.2009.700 · Cited by 185 · see citing works
Shen, L., & Turner, J. R. (2006) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00439.2005 · Cited by 176 · see citing works
Foley, S., Garsed, K. C., Singh, G., Duroudier, N. P., Swan, C., Hall, I. P., Zaitoun, A. M., Bennett, A. J., Marsden, C. A., Holmes, G. K. T., et al. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.01.052 · Cited by 140 · see citing works
Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome
Aerssens, J., Camilleri, M., Talloen, W., Thielemans, L., Göhlmann, H. W. H., Van den Wyngaert, I., Thielemans, T., De Hoogt, R., Andrews, C. N., Bharucha, A. E., et al. (2008) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2007.11.012 · Cited by 124 · see citing works
Origin of gas retention and symptoms in patients with bloating
Salvioli, B., Serra, J., Azpiroz, F., Lorenzo‐Bosquet, C., Aguadé‐Bruix, S., Castell‐Conesa, J., & Malagelada, J. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.12.047 · Cited by 122 · see citing works
Self-citationTurner, J. R. (2000) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00046-6 · Cited by 85 · see citing works
Impaired Small Bowel Gas Propulsion in Patients with Bloating During Intestinal Lipid Infusion
Salvioli, B., Serra, J., Azpiroz, F., & Malagelada, J. (2006) · The American Journal of Gastroenterology · doi:10.1111/j.1572-0241.2006.00702.x · Cited by 78 · see citing works
Self-citationSubjects with Diarrhea-Predominant IBS Have Increased Rectal Permeability Responsive to Tryptase
Lee, J. W., Park, J. H., Park, D. I. L., Park, J. H., Kim, H. J., Cho, Y. K., Sohn, C. I., Jeon, W. K., & Kim, B. I. (2010) · Digestive Diseases and Sciences · doi:10.1007/s10620-009-1094-8 · Cited by 68 · see citing works
Protease‐activated receptor 2 and gut permeability: a review
Bueno, L. P., & Fioramonti, J. (2008) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2008.01139.x · Cited by 67 · see citing works
Clinical update: irritable bowel syndrome
Spiller, R. E. (2007) · The Lancet · doi:10.1016/s0140-6736(07)60726-0 · Cited by 62 · see citing works
Malagelada, C., lorio, F. D., Seguí, S., Mendez, S., Drozdzal, M., Vitria, J. M., Radeva, P. I., Santos, J., Accarino, A. M., Malagelada, J., et al. (2011) · Neurogastroenterology & Motility · doi:10.1111/j.1365-2982.2011.01823.x · Cited by 38 · see citing works
Self-citationGraham, W. V., Marchiando, A. M., Shen, L., & Turner, J. R. (2009) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2009.04050.x · Cited by 10 · see citing works
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Bischoff, S. C., Barbara, G., Buurman, W., Ockhuizen, T., Schulzke, J.-D., Serino, M., Tilg, H., Watson, A., & Wells, J. M. (2014) · BMC Gastroenterology · doi:10.1186/s12876-014-0189-7 · Cited by 1,755 · see citing works
Enck, P., Aziz, Q., Barbara, G., Farmer, A. D., Fukudo, S., Mayer, E. A., Niesler, B., Quigley, E. M. M., Rajilić-Stojanović, M. D., Schemann, M., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.14 · Cited by 1,057 · see citing works
Michielan, A., & D’Incà, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/628157 · Cited by 709 · see citing works
Paracellular permeability and tight junction regulation in gut health and disease
Horowitz, A., Chánez-Paredes, S. D., Haest, X., & Turner, J. R. (2023) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00766-3 · Cited by 725 · see citing works
Pathophysiology of irritable bowel syndrome
Holtmann, G. J., Ford, A. C., & Talley, N. J. (2016) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(16)30023-1 · Cited by 590 · see citing works
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Vanheel, H., Vicario, M., Vanuytsel, T., Van Oudenhove, L., Martinez, C., Keita, Å. V., Pardon, N., Santos, J., Söderholm, J. D., Tack, J., et al. (2014) · Gut · doi:10.1136/gutjnl-2012-303857 · Cited by 424 · see citing works
Self-citationInflammatory and Microbiota-Related Regulation of the Intestinal Epithelial Barrier
Barbara, G., Barbaro, M. R., Fuschi, D., Palombo, M., Falangone, F., Cremon, C., Marasco, G., & Stanghellini, V. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.718356 · Cited by 420 · see citing works
Camilleri, M., Lasch, K. L., & Zhou, W. (2012) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00155.2012 · Cited by 397 · see citing works
The mucosal immune system: master regulator of bidirectional gut-brain communications
Powell, N., Walker, M. M., & Talley, N. J. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2016.191 · Cited by 379 · see citing works
Aburto, M. R., & Cryan, J. F. (2024) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-023-00890-0 · Cited by 391 · see citing works
Vivinus-Nébot, M., Frin-Mathy, G., Bzioueche, H., Dainese, R., Bernard, G., Anty, R., Filippi, J., Saint‐Paul, M., Tulić, M. K., Verhasselt, V., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-304066 · Cited by 365 · see citing works
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Fritscher-Ravens, A., Schuppan, D., Ellrichmann, M., Schoch, S., Röcken, C., Brasch, J., Bethge, J., Böttner, M., Klose, J., & Milla, P. J. (2014) · Gastroenterology · doi:10.1053/j.gastro.2014.07.046 · Cited by 329 · see citing works
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Self-citationChang, J., Leong, R. W., Wasinger, V. C., Ip, M., Yang, M., & Phan, T. G. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.05.056 · Cited by 286 · see citing works
The mucosal barrier at a glance
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The intestinal barrier function and its involvement in digestive disease
Salvo‐Romero, E., Alonso, C., Pardo‐Camacho, C., Casado‐Bedmar, M., & Vicario, M. (2015) · Revista Española de Enfermedades Digestivas · doi:10.17235/reed.2015.3846/2015 · Cited by 256 · see citing works
Self-citationGastrointestinal mucosal barrier function and diseases
Oshima, T., & Miwa, H. (2016) · Journal of Gastroenterology · doi:10.1007/s00535-016-1207-z · Cited by 250 · see citing works
Fritscher-Ravens, A., Pflaum, T., Mösinger, M., Ruchay, Z., Röcken, C., Milla, P. J., Das, M., Böttner, M., Wedel, T., & Schuppan, D. (2019) · Gastroenterology · doi:10.1053/j.gastro.2019.03.046 · Cited by 248 · see citing works
The intestinal microbiome, probiotics and prebiotics in neurogastroenterology
Saulnier, D. M., Ringel, Y., Heyman, M. B., Foster, J. A., Bercik, P., Shulman, R. J., Versalovic, J., Verdu, E. F., Dinan, T. G., Hecht, G., et al. (2013) · Gut Microbes · doi:10.4161/gmic.22973 · Cited by 248 · see citing works
Irritable bowel syndrome, the microbiota and the gut-brain axis
Raskov, H., Burcharth, J., Pommergaard, H.-C., & Rosenberg, J. (2016) · Gut Microbes · doi:10.1080/19490976.2016.1218585 · Cited by 243 · see citing works
Zhang, W., Xu, J., Yu, T., & Chen, Q. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.109131 · Cited by 246 · see citing works
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Irritable bowel syndrome: Emerging paradigm in pathophysiology
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Colonic immune cells in irritable bowel syndrome: A systematic review and meta‐analysis
Bashashati, M., Moossavi, S., Cremon, C., Barbaro, M. R., Moraveji, S., Talmon, G., Rezaei, N., Hughes, P. A., Bian, Z. X., Choi, C. H., et al. (2018) · Neurogastroenterology & Motility · doi:10.1111/nmo.13192 · Cited by 175 · see citing works
Cash, B. D., Epstein, M. S., & Shah, S. M. A. (2015) · Digestive Diseases and Sciences · doi:10.1007/s10620-015-3858-7 · Cited by 171 · see citing works
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Camilleri, M., Sellin, J. H., & Barrett, K. E. (2016) · Gastroenterology · doi:10.1053/j.gastro.2016.10.014 · Cited by 163 · see citing works
Bharucha, A. E., Batey-Schaefer, B., Cleary, P. A., Murray, J. A., Cowie, C., Lorenzi, G., Driscoll, M., Harth, J., Larkin, M., Christofi, M., et al. (2015) · Gastroenterology · doi:10.1053/j.gastro.2015.05.007 · Cited by 156 · see citing works
Piche, T. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12315 · Cited by 154 · see citing works
Putignani, L., CHIERICO, F. D., Vernocchi, P., Cicala, M., Cucchiara, S., & Dallapiccola, B. (2015) · Inflammatory Bowel Diseases · doi:10.1097/mib.0000000000000602 · Cited by 150 · see citing works
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Hughes, P. A., Zola, H., Penttila, I., Blackshaw, L. A., Andrews, J. M., & Krumbiegel, D. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.120 · Cited by 147 · see citing works
Skonieczna‐Żydecka, K., Marlicz, W. M., Misera, A., Koulaouzidis, A., & Łoniewski, I. (2018) · Journal of Clinical Medicine · doi:10.3390/jcm7120521 · Cited by 148 · see citing works
Martínez, C., Rodiño‐Janeiro, B. K., Lobo, B., Stanifer, M. L., Klaus, B., Granzow, M., González-Castro, A. M., Salvo‐Romero, E., Alonso, C., Pigrau, M., et al. (2017) · Gut · doi:10.1136/gutjnl-2016-311477 · Cited by 143 · see citing works
Self-citationWilcz‐Villega, E., McClean, S., & OʼSullivan, M. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.92 · Cited by 135 · see citing works
Cremon, C., Stanghellini, V., Barbaro, M. R., Cogliandro, R. F., Bellacosa, L., Santos, J., Vicario, M., Pigrau, M., Alonso, C., Lobo, B., et al. (2017) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13958 · Cited by 128 · see citing works
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Barmeyer, C., Schulzke, J. D., & Fromm, M. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.05.006 · Cited by 120 · see citing works
Pohl, C. S., Medland, J. E., Mackey, E. E., Edwards, L., Bagley, K., DeWilde, M., Williams, K. J., & Moeser, A. J. (2017) · Neurogastroenterology & Motility · doi:10.1111/nmo.13118 · Cited by 119 · see citing works
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Self-citationVicario, M., González-Castro, A. M., Martínez, C., Lobo, B., Pigrau, M., Guilarte, M., de Torres, I. M., Mosquera, J. L., Fortea, M., Sevillano-Aguilera, C., et al. (2014) · Gut · doi:10.1136/gutjnl-2013-306236 · Cited by 116 · see citing works
Self-citationMujagic, Z., de Vos, P., Boekschoten, M. V., Govers, C., Pieters, H., de Wit, N. J. W., Bron, P. A., Masclee, A., & Troost, F. J. (2017) · Scientific Reports · doi:10.1038/srep40128 · Cited by 108 · see citing works
Mujagic, Z., Ludidi, S., Keszthelyi, D., Hesselink, M., Kruimel, J. W., Lenaerts, K., Hanssen, N. M. J., Conchillo, J. M., Jonkers, D. M. A. E., & Masclee, A. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12829 · Cited by 108 · see citing works
Irritable bowel syndrome in children: Current knowledge, challenges and opportunities
Devanarayana, N. M., & Rajindrajith, S. (2018) · World Journal of Gastroenterology · doi:10.3748/wjg.v24.i21.2211 · Cited by 106 · see citing works
Mast cell mediation of visceral sensation and permeability in irritable bowel syndrome
Hasler, W. L., Grabauskas, G., Singh, P., & Owyang, C. (2022) · Neurogastroenterology & Motility · doi:10.1111/nmo.14339 · Cited by 105 · see citing works
Intestinal Barrier Permeability in Allergic Diseases
Niewiem, M., & Grzybowska‐Chlebowczyk, U. (2022) · Nutrients · doi:10.3390/nu14091893 · Cited by 107 · see citing works
No distinct microbiome signature of irritable bowel syndrome found in a Swedish random population
Hugerth, L. W., Andreasson, A., Talley, N. J., Forsberg, A. M., Kjellström, L., Schmidt, P. T., Agreus, L., & Engstrand, L. (2020) · Gut · doi:10.1136/gutjnl-2019-318717 · Cited by 102 · see citing works
Inflammation in irritable bowel syndrome: Myth or new treatment target?
Sinagra, E., Pompei, G., Tomasello, G., Cappello, F., Morreale, G. C., Amvrosiadis, G., Rossi, F., Monte, A. I. L., Rizzo, A. G., & Raimondo, D. (2016) · World Journal of Gastroenterology · doi:10.3748/wjg.v22.i7.2242 · Cited by 102 · see citing works
Carco, C., Young, W., Gearry, R. B., Talley, N. J., McNabb, W. C., & Roy, N. C. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00468 · Cited by 97 · see citing works
Dietary Lipids and Functional Gastrointestinal Disorders
Feinle‐Bisset, C., & Azpiroz, F. (2013) · The American Journal of Gastroenterology · doi:10.1038/ajg.2013.76 · Cited by 101 · see citing works
Self-citationInteractions between Innate Immunity, Microbiota, and Probiotics
Giorgetti, G., Brandimarte, G., Fabiocchi, F., Ricci, S., Flamini, P., Sandri, G., Trotta, M. C., Elisei, W., Penna, A., Lecca, P. G., et al. (2015) · Journal of Immunology Research · doi:10.1155/2015/501361 · Cited by 99 · see citing works
Dlugosz, A., Nowak, P., D’Amato, M., Kermani, G. M., Nyström, J., Abdurahman, S., & Lindberg, G. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12670 · Cited by 99 · see citing works
Autophagy and tight junction proteins in the intestine and intestinal diseases
Hu, C. A., Hou, Y., Yi, D., Qiu, Y., Wu, G., Kong, X., & Yin, Y. (2015) · Animal nutrition · doi:10.1016/j.aninu.2015.08.014 · Cited by 97 · see citing works
Lam, C., Tan, W., Leighton, M., Hastings, M. C., Lingaya, M. R., Falcone, Y., Zhou, X., Xu, L., Whorwell, P. J., Walls, A. F., et al. (2015) · Gut · doi:10.1136/gutjnl-2015-309122 · Cited by 92 · see citing works
Serum zonulin and its diagnostic performance in non-coeliac gluten sensitivity
Barbaro, M. R., Cremon, C., Morselli‐Labate, A. M., Sabatino, A. D., Giuffrida, P., Corazza, G. R., Stefano, M. D., Caio, G., Latella, G., Ciacci, C., et al. (2020) · Gut · doi:10.1136/gutjnl-2019-319281 · Cited by 88 · see citing works
Low-level inflammation, immunity, and brain-gut axis in IBS: unraveling the complex relationships
Yuan, Y., Wang, X., Huang, S., Wang, H., & Shen, G.-M. (2023) · Gut Microbes · doi:10.1080/19490976.2023.2263209 · Cited by 92 · see citing works
Lessons learned — resolving the enigma of genetic factors in IBS
Gazouli, M., Wouters, M. M., Kapur-Pojskić, L., Bengtson, M.-B., Friedman, E., Nikčević, G., Demetriou, C. A., Mulak, A., Santos, J., & Niesler, B. (2016) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.206 · Cited by 86 · see citing works
Self-citationThe Role of Mast Cells in Irritable Bowel Syndrome
Lee, K. N., & Lee, O. Y. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/2031480 · Cited by 88 · see citing works
Effect of commensals and probiotics on visceral sensitivity and pain in irritable bowel syndrome
Theodorou, V., Ait-Belgnaoui, A., Agostini, S., & Eutamene, H. (2014) · Gut Microbes · doi:10.4161/gmic.29796 · Cited by 83 · see citing works
Post-infectious IBS, tropical sprue and small intestinal bacterial overgrowth: the missing link
Ghoshal, U. C., & Gwee, K. (2017) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2017.37 · Cited by 82 · see citing works
Pigrau, M., Rodiño‐Janeiro, B. K., Casado‐Bedmar, M., Lobo, B., Vicario, M., Santos, J., & Alonso, C. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12717 · Cited by 79 · see citing works
Self-citationBuckley, M. M., O’Halloran, K. D., Rae, M. G., Dinan, T. G., & O’Malley, D. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.279968 · Cited by 74 · see citing works
Current insights into the innate immune system dysfunction in irritable bowel syndrome
Lazaridis, N. (2018) · Annals of Gastroenterology · doi:10.20524/aog.2018.0229 · Cited by 75 · see citing works
Butyrate Alleviates Cytokine-Induced Barrier Dysfunction by Modifying Claudin-2 Levels
Huang, X., Oshima, T., Tomita, T., Fukui, H., & Miwa, H. (2021) · Biology · doi:10.3390/biology10030205 · Cited by 72 · see citing works
Wilson, D., Evans, M., Weaver, E. M., Shaw, A. L., & Klein, G. L. (2013) · Clinical Medicine Insights Gastroenterology · doi:10.4137/cgast.s13200 · Cited by 70 · see citing works
Inflammatory bowel disease and irritable bowel syndrome
Barbara, G., Cremon, C., & Stanghellini, V. (2014) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000070 · Cited by 72 · see citing works
Xu, X., Zhang, Y. L., Liu, L., Pan, L., & Yao, S. (2016) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.13848 · Cited by 71 · see citing works
Irritable bowel syndrome, inflammatory bowel disease and the microbiome
Major, G., & Spiller, R. E. (2013) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000032 · Cited by 67 · see citing works
Abnormal Barrier Function in Gastrointestinal Disorders
Farré, R., & Vicario, M. (2016) · Handbook of experimental pharmacology · doi:10.1007/164_2016_107 · Cited by 67 · see citing works
Self-citationMarkers for visceral hypersensitivity in patients with irritable bowel syndrome
Ludidi, S., Mujagic, Z., Jonkers, D. M. A. E., Keszthelyi, D., Hesselink, M., Kruimel, J. W., Conchillo, J. M., & Masclee, A. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12365 · Cited by 66 · see citing works
Robles, A., Perez Ingles, D., Myneedu, K., Deoker, A., Sarosiek, I., Zuckerman, M. J., Schmulson, M. J., & Bashashati, M. (2019) · Neurogastroenterology & Motility · doi:10.1111/nmo.13718 · Cited by 65 · see citing works
High FODMAP diet causes barrier loss via lipopolysaccharide-mediated mast cell activation
Singh, P., Grabauskas, G., Zhou, S.-Y., Gao, J., Zhang, Y., & Owyang, C. (2021) · JCI Insight · doi:10.1172/jci.insight.146529 · Cited by 65 · see citing works
Functional abdominal pain disorders in children
Rajindrajith, S., Zeevenhooven, J., Devanarayana, N. M., Perera, B. J. C., & Benninga, M. A. (2018) · Expert Review of Gastroenterology & Hepatology · doi:10.1080/17474124.2018.1438188 · Cited by 64 · see citing works
Abdulnour‐Nakhoul, S. M., Al‐Tawil, Y., Gyftopoulos, A. A., Brown, K., Hansen, M., Butcher, K. F., Eidelwein, A. P., Noel, R. A., Rabon, E., Posta, A., et al. (2013) · Clinical Immunology · doi:10.1016/j.clim.2013.05.004 · Cited by 63 · see citing works
González-Castro, A. M., Martínez, C., Salvo‐Romero, E., Fortea, M., Pardo‐Camacho, C., Pérez, T., Alonso, C., Santos, J., & Vicario, M. (2016) · Journal of Gastroenterology and Hepatology · doi:10.1111/jgh.13417 · Cited by 64 · see citing works
Self-citationLobo, B., Ramos, L., Martínez, C., Guilarte, M., González-Castro, A. M., Alonso, C., Pigrau, M., de Torres, I. M., Rodiño‐Janeiro, B. K., Salvo‐Romero, E., et al. (2017) · United European Gastroenterology Journal · doi:10.1177/2050640617691690 · Cited by 62 · see citing works
Self-citationReed, C. C., Genta, R. M., Youngblood, B. A., Wechsler, J. B., & Dellon, E. S. (2020) · Clinical Gastroenterology and Hepatology · doi:10.1016/j.cgh.2020.08.013 · Cited by 63 · see citing works
Camilleri, M., Carlson, P., Acosta, A. J., Busciglio, I. A., Nair, A., Gibbons, S. J., Farrugia, G., & Klee, E. W. (2014) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00068.2014 · Cited by 60 · see citing works
Intestinal epithelial barrier and neuromuscular compartment in health and disease
D’Antongiovanni, V., Pellegrini, C., Fornai, M., Colucci, R., Blandizzi, C., Antonioli, L., & Bernardini, N. (2020) · World Journal of Gastroenterology · doi:10.3748/wjg.v26.i14.1564 · Cited by 59 · see citing works
Wu, Y., Li, Y., Zheng, Q., & Li, L. (2024) · Nutrients · doi:10.3390/nu16132114 · Cited by 66 · see citing works
Martin‐Viñas, J. J., & Quigley, E. M. M. (2016) · Journal of Digestive Diseases · doi:10.1111/1751-2980.12379 · Cited by 57 · see citing works
Starring role of toll-like receptor-4 activation in the gut-liver axis
Carotti, S. (2015) · World Journal of Gastrointestinal Pathophysiology · doi:10.4291/wjgp.v6.i4.99 · Cited by 57 · see citing works
Duodenal inflammation: an emerging target for functional dyspepsia?
Wauters, L. I., Burns, G. L., Ceulemans, M., Walker, M. M., Vanuytsel, T., Keely, S., & Talley, N. J. (2020) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2020.1752181 · Cited by 56 · see citing works
Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome
Keszthelyi, D., Troost, F. J., Jonkers, D. M. A. E., van Eijk, H. M. H., Lindsey, P. J., Dekker, J. P., Buurman, W. A., & Masclee, A. (2014) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.12842 · Cited by 53 · see citing works
Wu, R. L., Vázquez‐Roque, M. I., Carlson, P., Burton, D. D., Grover, M., Camilleri, M., & Turner, J. R. (2016) · Laboratory Investigation · doi:10.1038/labinvest.2016.118 · Cited by 54 · see citing works
He, G., Zhang, T., Zhou, X., Liu, X., Sun, H., Chen, Y., Tan, B., & Lin, S. (2022) · Aquaculture Reports · doi:10.1016/j.aqrep.2022.101052 · Cited by 53 · see citing works
Using human intestinal biopsies to study the pathogenesis of irritable bowel syndrome
Nasser, Y., Boeckxstaens, G. E., Wouters, M. M., Schemann, M., & Vanner, S. J. (2014) · Neurogastroenterology & Motility · doi:10.1111/nmo.12316 · Cited by 53 · see citing works
Zhu, H., Xiao, X., Shi, Y., Wu, Y., Huang, Y., Li, D., Xiong, F., He, G., Chai, Y., & Tang, H. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.9284 · Cited by 53 · see citing works
Immune responses in the irritable bowel syndromes: time to consider the small intestine
Burns, G. L., Talley, N. J., & Keely, S. (2022) · BMC Medicine · doi:10.1186/s12916-022-02301-8 · Cited by 54 · see citing works
Wilcz‐Villega, E., McClean, S., & OʼSullivan, M. (2013) · Neurogastroenterology & Motility · doi:10.1111/nmo.12262 · Cited by 52 · see citing works
Linsalata, M., Riezzo, G., Clemente, C., D’Attoma, B., & Russo, F. (2020) · Disease Markers · doi:10.1155/2020/2886268 · Cited by 50 · see citing works
Present and Future Therapeutic Approaches to Barrier Dysfunction
Fortea, M., Albert-Bayo, M., Abril-Gil, M., Mall, J. G., Serra-Ruiz, X., Henao-Paez, A., Expósito, E., González-Castro, A. M., Guagnozzi, D., Lobo, B., et al. (2021) · Frontiers in Nutrition · doi:10.3389/fnut.2021.718093 · Cited by 48 · see citing works
Self-citationPsychosocial stress-induced intestinal permeability in healthy humans: What is the evidence?
Torre, D. L., Oudenhove, L. V., Vanuytsel, T., & Verbeke, K. (2023) · Neurobiology of Stress · doi:10.1016/j.ynstr.2023.100579 · Cited by 52 · see citing works
Tryptase and Protease-Activated Receptor 2 Expression Levels in Irritable Bowel Syndrome
Liang, W.-J., Zhang, G., Luo, H.-S., Liang, L., Huang, D., & Zhang, F.-C. (2015) · Gut and Liver · doi:10.5009/gnl14319 · Cited by 49 · see citing works
A meta‐analysis of immunogenetic Case–Control Association Studies in irritable bowel syndrome
Czogalla, B., Schmitteckert, S., Houghton, L. A., Sayuk, G. S., Camilleri, M., Olivo‐Diaz, A., Spiller, R., Wouters, M. M., Boeckxstaens, G., Lorenzo Bermejo, J., et al. (2015) · Neurogastroenterology & Motility · doi:10.1111/nmo.12548 · Cited by 48 · see citing works
Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS
Törnblom, H., Oudenhove, L. V., Tack, J. F., & Simrén, M. (2013) · Gut · doi:10.1136/gutjnl-2013-305853 · Cited by 48 · see citing works
Subacute stress and chronic stress interact to decrease intestinal barrier function in rats
Lauffer, A., Vanuytsel, T., Vanormelingen, C., Vanheel, H., Rasoel, S. S., Tóth, J. G., Tack, J. F., Fornari, F., & Farré, R. (2016) · Stress · doi:10.3109/10253890.2016.1154527 · Cited by 47 · see citing works
Endoscopy-Guided Evaluation of Duodenal Mucosal Permeability in Functional Dyspepsia
Ishigami, H., Matsumura, T., Kasamatsu, S., Hamanaka, S., Taida, T., Okimoto, K., Saito, K., Minemura, S., Maruoka, D., Nakagawa, T., et al. (2017) · Clinical and Translational Gastroenterology · doi:10.1038/ctg.2017.12 · Cited by 47 · see citing works
Du, L., Kim, J. J., Shen, J., & Dai, N. (2016) · Gastroenterology Research and Practice · doi:10.1155/2016/7374197 · Cited by 46 · see citing works
- Authors
- Martínez, C., Lobo, B., Pigrau, M., Ramos, L., González-Castro, A. M., Alonso, C., Guilarte, M., Guilá, M., de Torres, I., Azpiroz, F., Santos, J., & Vicario, M.
- Affiliations
- Universitat Autònoma de Barcelona (ES)
- Department of Gastroenterology, Digestive System Research Unit, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona (Departmento de Medicina), Barcelona, Spain
- Pathology Department, Hospital Universitari Vall d'Hebron and Vall d'Hebron Institut de Recerca, Universitat Autònoma de Barcelona (Departmento de Medicina), Barcelona, Spain
- Corresponding author
- Vicario, María
- ORCID
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2012-05-25
- Volume
- 62
- Issue
- 8
- Pages
- 1160-1168
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- OpenAlex
- W2111819970
- Cited by
- 283
- References
- 44
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 15 · 2023: 11 · 2022: 26 · 2021: 20 · 2020: 24 · 2019: 23 · 2018: 15 · 2017: 26 · 2016: 32 · 2015: 20 · 2014: 30 · 2013: 18 · 2012: 3
- FWCI
- 22.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gut (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- diarrhea-predominant irritable bowel syndrome, mast cell activation, claudin-2, occludin phosphorylation, myosin phosphatase, tryptase, CD117, jejunal mucosa, functional gastrointestinal disorders
- MeSH terms
- Adolescent, Adult, Biopsy, Diarrhea, Female, Humans, Intercellular Junctions, Intestinal Mucosa, Jejunum, Male, Mast Cells, Middle Aged, Phosphorylation, Prospective Studies, Sex Factors, Stress, Psychological, Myosin Light Chains, Irritable Bowel Syndrome, Young Adult, Tight Junction Proteins
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