Zonulin is a protein that modulates the permeability of tight junctions between cells of the wall of the digestive tract. Initially discovered in 2000 as the target of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, it has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1.
Gliadin (glycoprotein present in wheat) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules. ALBA Therapeutics is developing a zonulin receptor antagonist, Larazotide acetate (formerly known as AT-1001), that successfully passed phase 2b clinical trials.
Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines.
- 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
- Lemmer HJ, Hamman JH. Paracellular drug absorption enhancement through tight junction modulation. Expert Opin Drug Deliv. 2013 Jan;10(1):103-14. PMID 23163247
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