Intestinal permeability is the phenomenon of the gut wall in the gastrointestinal tract exhibiting permeability. It is a normal function of the intestine to exhibit some permeability, to allow nutrients to pass through the gut, while also maintaining a barrier function to keep potentially harmful substances (such as antigens) from leaving the intestine and migrating to the body more widely. In a healthy human intestine, small particles (< 4 Å in radius) can migrate through tight junction claudin pore pathways, and particles up to 10-15 Å (3.5 kDa) can transit through the paracellular space uptake route.
One way in which intestinal permeability is modulated is via CXCR3 receptors in the gut wall, which respond to zonulin. Gliadin (glycoprotein present in wheat) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules. Bacterial pathogens such as cholera, select enteric viruses, parasites modulate intestinal tight junction structure and function, and these effects may contribute to the development of chronic intestinal disorders.
Excessive intestinal permeability is a factor in several autoimmune conditions such as Crohn's disease, celiac disease, type 1 diabetes, and inflammatory bowel disease,  but it is not clear if increased intestinal permeability is a cause or a consequence of these conditions. Larazotide acetate (previously known as AT-1001) is a zonulin receptor antagonist drug candidate that is in clinical trials for celiac disease, based on the hypothesis that increased intestinal permeability in coeliac is harmful to health.
A proposed medical condition called leaky gut syndrome has been popularized which theorizes that restoring normal functioning of the gut wall can cure many systemic health conditions, but there is little evidence to support this theory, and no evidence that so-called 'treatments' for 'leaky gut syndrome', such as nutritional supplements and a gluten-free diet, have any beneficial effect for most of the conditions they are claimed to help.
- M. Campieri; C. Fiocchi; S.B. Hanauer (31 March 2002). Inflammatory Bowel Disease: A Clinical Case Approach to Pathophysiology, Diagnosis, and Treatment. Springer. p. 7. ISBN 978-0-7923-8772-5.
- Thoma YM, Anderson JM, Turner JR (2012). Johnson LR, et al, ed. Tight Junctions and the Intestinal Barrier. Physiology of the Gastrointestinal Tract 1 (Academic Press). pp. 1043–. ISBN 978-0-12-382027-3.
- Fasano, A. (February 2012). "Leaky Gut and Autoimmune Diseases". Clinical Reviews in Allergy & Immunology 42 (1): 71–78. doi:10.1007/s12016-011-8291-x. PMID 22109896.
- Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011 Jan;91(1):151-75. PMID 21248165
- O'Hara, JR; Buret, AG (2008). "Mechanisms of intestinal tight junctional disruption during infection". Frontiers in Bioscience 13: 7008. doi:10.2741/3206. PMID 18508712.
- "Leaky gut syndrome". NHS Choices. 9 April 2013. Retrieved 24 October 2013.
- Heyman M et al. Intestinal permeability in coeliac disease: insight into mechanisms and relevance to pathogenesis. Gut. 2012 Sep;61(9):1355-64. PMID 21890812
- Crespo Pérez L et al. Non-dietary therapeutic clinical trials in coeliac disease. Eur J Intern Med. 2012 Jan;23(1):9-14. PMID 22153524