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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,[1] it has been implicated in the pathogenesis of coeliac disease[2] and diabetes mellitus type 1.[3] It is being studied as a target for vaccine adjuvants.[4] ALBA Therapeutics is developing a zonulin receptor antagonist, AT-1001, that is currently in phase 2 clinical trials.

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


  1. ^ Wang, W; Uzzau, S; Goldblum, SE; Fasano, A (2000). "Human zonulin, a potential modulator of intestinal tight junctions". Journal of Cell Science 113 (24): 4435–40. PMID 11082037. 
  2. ^ Thomas, KE; Sapone, A; Fasano, A; Vogel, SN (2006). "Gliadin stimulation of murine macrophage inflammatory gene expression and intestinal permeability are MyD88-dependent: role of the innate immune response in Celiac disease". Journal of immunology (Baltimore, Md. : 1950) 176 (4): 2512–21. PMID 16456012. 
  3. ^ Sapone, A; De Magistris, L; Pietzak, M; Clemente, MG; Tripathi, A; Cucca, F; Lampis, R; Kryszak, D; Cartenì, M; Generoso, M; Iafusco, D; Prisco, F; Laghi, F; Riegler, G; Carratu, R; Counts, D; Fasano, A (2006). "Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives". Diabetes 55 (5): 1443–9. doi:10.2337/db05-1593. PMID 16644703. 
  4. ^ De Magistris, MT (2006). "Zonula occludens toxin as a new promising adjuvant for mucosal vaccines". Vaccine. 24 Suppl 2: S2–60–1. PMID 16823929. 
  5. ^ Drago, Sandro; El Asmar, Ramzi El; Di Pierro, Mariarosaria; Grazia Clemente, Maria Grazia; Tripathi, Amit Tripathi Anna; Sapone, Manjusha; Thakar, Giuseppe; Iacono, Antonio; Carroccio, Cinzia D'Agate Tarcisio; d'Agate, Lucia; Not, Catassi; Zampini, Alessio; Catassi, C; Fasano, A (2006). "Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines". Scandinavian Journal of Gastroenterology 41 (4): 408–419. doi:10.1080/00365520500235334. PMID 16635908.