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Zonulin 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]

Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines.[3] In February a zonulin receptor antagonist, Larazotide acetate (formerly known as AT-1001), completed a phase 2b clinical trial.[4]


  1. ^ Vanuytsel T, et al. The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease. Tissue Barriers. 2013 Dec 1;1(5):e27321. doi: 10.4161/tisb.27321. Epub 2013 Dec 10. PMCID PMC3943850 PMID 24868498
  2. ^ a b 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
  3. ^ Lemmer HJ, Hamman JH. Paracellular drug absorption enhancement through tight junction modulation. Expert Opin Drug Deliv. 2013 Jan;10(1):103-14. PMID 23163247
  4. ^ "Alba Therapeutics announces positive results of phase IIb trial in celiac disease" (Press release). Alba Therapeutics. February 11, 2014.