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Alessio Fasano
Zonulin (haptoglobin 2 precursor)[1] is aprotein that increases the permeability oftight junctions betweencells of the wall of thedigestive tract.[2] It was discovered in 2000 byAlessio Fasano and his team at theUniversity of Maryland School of Medicine. As the mammalian analogue ofzonula occludens toxin, secreted bycholera pathogenVibrio cholerae, zonulin has been implicated in the pathogenesis ofcoeliac disease anddiabetes mellitus type 1.[3]Type 2 diabetic patients have shown increased zonulin.[4] However, in recent years, researchers in the field have called into question the existence of zonulin after discovering that the popular ELISA assay used to measure zonulin may have in fact been measuring different proteins across studies. These observations have led some in the field to conclude that zonulin is an ill-defined term encompassing potentially many different proteins and is therefore a poor biomarker of celiac disease.[5]
Gliadin (a glycoprotein present ingluten) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increasedintestinal permeability of macromolecules.[3][6]
Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines.[7] In 2014 a zonulinreceptor antagonist,larazotide acetate (formerly known as AT-1001), completed aphase 2b clinical trial.[8][9]
