How Cholera Research Uncovered Zonulin

Alessio Fasano, MD, was researching cholera when the research in his lab revealed a new factor contributing to intestinal permeability: zonulin.1 Zonulin is a protein and a mechanism by which intestinal permeability is increased in the body, increasing the space between tight junctions in the intestines.2 Zonulin’s regulatory functions in the gut also affect many chronic illnesses.3-6

“When you push the limits, you spill from physiology to pathology.” – Alessio Fasano

Patrick Hanaway, MD, director of research at the Cleveland Clinic Center for Functional Medicine, interviews Alessio Fasano, MD and researcher.

In this interview with Patrick Hanaway, MD, Dr. Fasano describes how the path to uncovering zonulin was one of serendipity and open-mindedness. Dr. Fasano won the Linus Pauling Award from IFM in 2013.


  1. Wang W, Uzzau S, Goldblum SE, Fasano A. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000;113(Pt 24):4435-4440.
  2. Tripathi A, Lammers KM, Goldblum S, et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc Natl Acad Sci U S A. 2009;106(39):16799-16804. doi:1073/pnas.0906773106.
  3. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016;4(4):e1251384. doi:1080/21688370.2016.1251384.
  4. Fasano A. Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer. Physiol Rev. 2011;91(1):151-175. doi:1152/physrev.00003.2008.
  5. Dschietzig TB, Boschann F, Ruppert J, et al. Plasma zonulin and its association with kidney function, severity of heart failure, and metabolic inflammation. Clin Lab. 2016;62(12):2443-2447. doi:7754/Clin.Lab.2016.160512.
  6. Vanuytsel T, Vermeire S, Cleynen I. The role of haptoglobin and its related protein, zonulin, in inflammatory bowel disease. Tissue Barriers. 2013;1(5):e27321. doi:4161/tisb.27321.
  7. Malícková K, Francová I, Lukáš M, et al. Fecal zonulin is elevated in Crohn’s disease and in cigarette smokers. Pract Lab Med. 2017;9:39-44. doi:1016/j.plabm.2017.09.001.

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