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Zonulin syn. Haptoglobin (http://www.uniprot.org/uniprot/P00738)[permanent dead link] is a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract.[1] It was discovered in 2000 by Alessio Fasano and his team at the University of Maryland School of Medicine. As the mammalian analogue of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, zonulin has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1.[2]

Gliadin (glycoprotein present in wheat) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.[2][3][4][5]

Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines.[6] In 2014 a zonulin receptor antagonist, Larazotide acetate (formerly known as AT-1001), completed a phase 2b clinical trial.[7]

Giovanni Barbara and a team of researchers at the University of Bologna measured blood levels of zonulin in four groups of individuals: those with Celiac Disease, those with irritable bowel syndrome marked by diarrhea, those with self-diagnosed gluten sensitivity and healthy volunteers. Both celiacs and gluten-sensitives turned up with remarkably high levels of zonulin in their blood. Those with IBS had elevated levels but less than half the levels of celiacs or gluten-sensitive individuals. Healthy volunteers had negligible blood levels of zonulin. The results were presented in October as an abstract at the 23rd United European Gastroenterology Week in Barcelona, Spain. "I was very surprised, but not only by the zonulin levels," says Barbara. "In our study, gluten-sensitive individuals who responded to a gluten-free diet had a genetic predisposition to celiac disease. They had no evidence of celiac, but they did have the vulnerable genes that put a person at risk of celiac."[8]


  1. ^ Vanuytsel, T; et al. (Dec 2013). "The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease". Tissue Barriers. 1 (5): e27321. doi:10.4161/tisb.27321. PMID 24868498. 
  2. ^ a b Fasano, A (Jan 2011). "Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer". Physiol Rev. 91 (1): 151–75. doi:10.1152/physrev.00003.2008. PMID 21248165. 
  3. ^ Lammers, Karen M.; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir (2008-07-01). "Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3". Gastroenterology. 135 (1): 194–204.e3. doi:10.1053/j.gastro.2008.03.023. ISSN 1528-0012. PMC 2653457free to read. PMID 18485912. 
  4. ^ Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio (2009-05-01). "Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms". Annals of the New York Academy of Sciences. 1165: 195–205. doi:10.1111/j.1749-6632.2009.04037.x. ISSN 0077-8923. PMC 2886850free to read. PMID 19538307. 
  5. ^ Fasano, Alessio (2011-01-01). "Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer". Physiological Reviews. 91 (1): 151–175. doi:10.1152/physrev.00003.2008. ISSN 0031-9333. PMID 21248165. 
  6. ^ Lemmer, HJ; Hamman, JH (Jan 2013). "Paracellular drug absorption enhancement through tight junction modulation". Expert Opin Drug Deliv. 10 (1): 103–14. doi:10.1517/17425247.2013.745509. PMID 23163247. 
  7. ^ "Alba Therapeutics announces positive results of phase IIb trial in celiac disease" (Press release). Alba Therapeutics. February 11, 2014. 
  8. ^ http://www.npr.org/sections/thesalt/2015/12/09/459061317/a-protein-in-the-gut-may-explain-why-some-cant-stomach-gluten?utm_medium=RSS&utm_campaign=food