What is “leaky gut”?

Bronwyn Hamilton, MD
What is "leaky gut"?


Leaky gut can be explained as having abnormally increased intestinal permeability. This is a state where the digested food fragments in our gut can get into our bloodstream through gaps (called tight junctions) between the single cells lining our gut are abnormally “leaky”. These incompletely digested food fragments should not be in our blood, since they activate the immune system, which perceives them as an infectious threat, and starts to attack. Gluten ingestion is not the only cause of this, and many things may increase intestinal permeability, for example, chronic drug use, radiation treatment, and alcohol abuse, among others. This appears to be particularly problematic for individuals genetically prone to autoimmunity. The best research on this topic has been done by Dr. Alessio Fasano at Massachusetts General Hospital who has shown that gluten increases intestinal permeability even in normal individuals1,2. However, for normal individuals, this phenomenon appears transient without apparent risk for long-term complications.

Dr. Fasano’s original research arose from his work on cholera, a severe infectious diarrheal illness (due to Vibrio Cholera) that also causes leaky gut and has a high fatality rate in severe untreated cases. In 2000, Dr. Fasano’s group reported the discovery of zonulin, a human protein analogue of the Vibrio cholerae-derived Zonula occludens toxin, that plays a crucial role in regulating intestinal permeability3. Increased zonulin is a hallmark of untreated celiac disease, but is seen in other disorders, especially autoimmune disorders in general.

Since these discoveries, it has been observed that many chronic inflammatory disorders have increased intestinal permeability and that elevated zonulin affects other organs besides the gastrointestinal tract, including the central nervous system, where it can cause increased blood-brain barrier permeability4,5. This results in blood vessel “leakiness” in the brain that also leads to inflammation there that over the long term may contribute to the development of many disorders, including things like neuropathy and ataxia, as well as neurodegenerative disorders.

For more information on “leaky gut” there is a great educational YouTube video by Dr. Fasano explaining this:


  1. 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.
  2. Fasano A. Zonulin, regulation of tight junctions, and autoimmune diseases. Ann N Y Acad Sci. 2012 Jul;1258(1):25-33.
  3. Fasano A, Not T, Wang W, Uzzau S, Berti I, Tommasini A, Goldblum SE. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9.
  4. Sturgeon C, Fasano A. Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases. Tissue Barriers. 2016 Oct 21;4(4):e1251384.
  5. Veres-Székely A, Szász C, Pap D, Szebeni B, Bokrossy P, Vannay Á. Zonulin as a Potential Therapeutic Target in Microbiota-Gut-Brain Axis Disorders: Encouraging Results and Emerging Questions. Int J Mol Sci. 2023 Apr 19;24(8):7548.

Published January 8, 2024

Note: This information is provided by NCA and Bronwyn Hamilton, MD. This information is meant for educational purposes only and is not intended to substitute for personalized medical advice or replace any medical advice provided directly to you by your health care provider. No liability is assumed by the NCA or Bronwyn Hamilton, MD by providing this information.

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