Zonulin (haptoglobin 2 precursor) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

that increases the permeability of

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

s between cells of the wall of the

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...

. It was discovered in 2000 by

Alessio Fasano Alessio Fasano is an Italian-born medical doctor, pediatric gastroenterologist and researcher. He currently holds many roles, including professor of pediatrics at Harvard Medical School and professor of nutrition at Harvard T.H. Chan School of P ...

and his team at the

University of Maryland School of Medicine The University of Maryland School of Medicine (abbreviated UMSOM), located in Baltimore City, Maryland, U.S., is the medical school of the University of Maryland, Baltimore and is affiliated with the University of Maryland Medical Center and Me ...

. As the mammalian analogue of zonula occludens toxin, secreted by

cholera Cholera is an infection of the small intestine by some strains of the bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea that lasts a few days. Vomiting and ...

pathogen ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and oth ...

'', zonulin has been implicated in the pathogenesis of

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barle ...

and

diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

. Type 2 diabetic patients have shown increased zonulin.

Gliadin Gliadin (a type of prolamin) is a class of proteins present in wheat and several other cereals within the grass genus ''Triticum''. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during baki ...

(a glycoprotein present in

gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all grain ...

) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability of macromolecules. Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines. In 2014 a zonulin

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rece ...

larazotide acetate Larazotide (INN; also known as AT-1001; formulated as the salt with acetic acid, larazotide acetate) is a synthetic eight amino acid peptide that functions as a tight junction regulator and reverses leaky junctions to their normally closed state ...

(formerly known as AT-1001), completed a phase 2b clinical trial.{{cite journal , last1=Leffler , first1=DA , last2=Kelly , first2=CP , last3=Green , first3=PH , last4=Fedorak , first4=RN , last5=DiMarino , first5=A , last6=Perrow , first6=W , last7=Rasmussen , first7=H , last8=Wang , first8=C , last9=Bercik , first9=P , last10=Bachir , first10=NM , last11=Murray , first11=JA , title=Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. , journal=Gastroenterology , date=June 2015 , volume=148 , issue=7 , pages=1311-9.e6 , doi=10.1053/j.gastro.2015.02.008 , pmid=25683116, pmc=4446229

References

Digestive system

See also

References