Simon, D. B. et al. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ resorption. Science 285, 103–106 (1999).

Article  CAS  PubMed  Google Scholar 

Kausalya, P. J. et al. Disease-associated mutations affect intracellular traffic and paracellular Mg2+ transport function of claudin-16. J. Clin. Invest. 116, 878–891 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wilcox, E. R. et al. Mutations in the gene encoding tight junction claudin-14 cause autosomal recessive deafness DFNB29. Cell 104, 165–172 (2001).

Article  CAS  PubMed  Google Scholar 

Ben-Yosef, T. et al. Claudin 14 knockout mice, a model for autosomal recessive deafness DFNB29, are deaf due to cochlear hair cell degeneration. Hum. Mol. Genet. 12, 2049–2061 (2003).

Article  CAS  PubMed  Google Scholar 

Zhao, J. et al. Multiple claudin–claudin cis interfaces are required for tight junction strand formation and inherent flexibility. Commun. Biol. 1, 50 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Wattenhofer, M. et al. Different mechanisms preclude mutant CLDN14 proteins from forming tight junctions in vitro. Hum. Mutat. 25, 543–549 (2005).

Article  CAS  PubMed  Google Scholar 

Hooper, L. V., Littman, D. R. & Macpherson, A. J. Interactions between the microbiota and the immune system. Science 336, 1268–1273 (2012).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Buckley, A. & Turner, J. R. Cell biology of tight junction barrier regulation and mucosal disease. Cold Spring Harb. Perspect. Biol. 10, a029314 (2018).

Article  PubMed  PubMed Central  Google Scholar 

Wada, M., Tamura, A., Takahashi, N. & Tsukita, S. Loss of claudins 2 and 15 from mice causes defects in paracellular Na+ flow and nutrient transport in gut and leads to death from malnutrition. Gastroenterology 144, 369–380 (2013).

Article  CAS  PubMed  Google Scholar 

Odenwald, M. A. & Turner, J. R. Intestinal permeability defects: is it time to treat? Clin. Gastroenterol. Hepatol. 11, 1075–1083 (2013).

Article  PubMed  PubMed Central  Google Scholar 

Odenwald, M. A. & Turner, J. R. The intestinal epithelial barrier: a therapeutic target? Nat. Rev. Gastroenterol. Hepatol. 14, 9–21 (2017).

Article  CAS  PubMed  Google Scholar 

Camilleri, M. Leaky gut: mechanisms, measurement and clinical implications in humans. Gut 68, 1516–1526 (2019).

Article  CAS  PubMed  Google Scholar 

Brien, T. G., O’Hagan, R. & Muldowney, F. P. Chromium-51-EDTA in the determination of glomerular filtration rate. Acta Radiol. Ther. Phys. Biol. 8, 523–529 (1969).

Article  CAS  PubMed  Google Scholar 

Ukabam, S. O., Clamp, J. R. & Cooper, B. T. Abnormal small intestinal permeability to sugars in patients with Crohn’s disease of the terminal ileum and colon. Digestion 27, 70–74 (1983).

Article  CAS  PubMed  Google Scholar 

Howden, C. W., Robertson, C., Duncan, A., Morris, A. J. & Russell, R. I. Comparison of different measurements of intestinal permeability in inflammatory bowel disease. Am. J. Gastroenterol. 86, 1445–1449 (1991).

CAS  PubMed  Google Scholar 

Peeters, M. et al. Increased permeability of macroscopically normal small bowel in Crohn’s disease. Dig. Dis. Sci. 39, 2170–2176 (1994).

Article  CAS  PubMed  Google Scholar 

Johansson, J. E. & Ekman, T. Gut toxicity during hemopoietic stem cell transplantation may predict acute graft-versus-host disease severity in patients. Dig. Dis. Sci. 52, 2340–2345 (2007).

Article  PubMed  Google Scholar 

Wyatt, J., Vogelsang, H., Hubl, W., Waldhoer, T. & Lochs, H. Intestinal permeability and the prediction of relapse in Crohn’s disease. Lancet 341, 1437–1439 (1993).

Article  CAS  PubMed  Google Scholar 

D’Inca, R. et al. Intestinal permeability test as a predictor of clinical course in Crohn’s disease. Am. J. Gastroenterol. 94, 2956–2960 (1999).

Article  PubMed  Google Scholar 

Bitton, A. et al. Predicting relapse in Crohn’s disease: a biopsychosocial model. Gut 57, 1386–1392 (2008).

Article  CAS  PubMed  Google Scholar 

Meddings, J. B. & Swain, M. G. Environmental stress-induced gastrointestinal permeability is mediated by endogenous glucocorticoids in the rat. Gastroenterology 119, 1019–1028 (2000).

Article  CAS  PubMed  Google Scholar 

Buhner, S. et al. Genetic basis for increased intestinal permeability in families with Crohn’s disease: role of CARD15 3020insC mutation? Gut 55, 342–347 (2006).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Torres, J. et al. Serum biomarkers identify patients who will develop inflammatory bowel diseases up to 5 years before diagnosis. Gastroenterology 159, 96–104 (2020).

Article  CAS  PubMed  Google Scholar 

Turpin, W. et al. Increased intestinal permeability is associated with later development of Crohn’s disease. Gastroenterology 159, 2092–2100.e5 (2020).

Article  CAS  PubMed  Google Scholar 

Lee, S. H. et al. Anti-microbial antibody response is associated with future onset of Crohn’s disease independent of biomarkers of altered gut barrier function, subclinical inflammation, and genetic risk. Gastroenterology 161, 1540–1551 (2021).

Article  CAS  PubMed  Google Scholar 

Edwinson, A. L. et al. Gut microbial β-glucuronidases regulate host luminal proteases and are depleted in irritable bowel syndrome. Nat. Microbiol. 7, 680–694 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Camilleri, M. & Gorman, H. Intestinal permeability and irritable bowel syndrome. Neurogastroenterol. Motil. 19, 545–552 (2007).

Article  CAS  PubMed  Google Scholar 

Edogawa, S. et al. Serine proteases as luminal mediators of intestinal barrier dysfunction and symptom severity in IBS. Gut 69, 62–73 (2020).

Article  CAS  PubMed  Google Scholar 

de Magistris, L. et al. Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J. Pediatr. Gastroenterol. Nutr. 51, 418–424 (2010).

Article  PubMed  Google Scholar 

Hsiao, E. Y. et al. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155, 1451–1463 (2013).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Inczefi, O. et al. Targeted intestinal tight junction hyperpermeability alters the microbiome, behavior, and visceromotor responses. Cell Mol. Gastroenterol. Hepatol. 10, 206–208.e3 (2020).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farquhar, M. & Palade, G. Junctional complexes in various epithelia. J. Cell Biol. 17, 375–412 (1963).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Stevenson, B. R., Siliciano, J. D., Mooseker, M. S. & Goodenough, D. A. Identification of ZO-1: a high molecular weight polypeptide associated with the tight junction (zonula occludens) in a variety of epithelia. J. Cell Biol. 103, 755–766 (1986).

Article  CAS  PubMed  Google Scholar 

Stevenson, B. R., Heintzelman, M. B., Anderson, J. M., Citi, S. & Mooseker, M. S. ZO-1 and cingulin: tight junction proteins with distinct identities and localizations. Am. J. Physiol. 257, C621–C628 (1989).

Article  CAS  PubMed  Google Scholar 

Jesaitis, L. A. & Goodenough, D. A. Molecular characterization and tissue distribution of ZO-2, a tight junction protein homologous to ZO-1 and the Drosophila discs-large tumor suppressor protein. J. Cell Biol. 124, 949–961 (1994).

Article  CAS  PubMed  Google Scholar 

Haskins, J., Gu, L., Wittchen, E. S., Hibbard, J. & Stevenson, B. R. ZO-3, a novel member of the MAGUK protein family found at the tight junction, interacts with ZO-1 and occludin. J. Cell Biol. 141, 199–208 (1998).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Citi, S., Sabanay, H., Jakes, R., Geiger, B. & Kendrick-Jones, J. Cingulin, a new peripheral component of tight junctions. Nature 333, 272–276 (1988).