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Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases
Open accessAbstract
Beside digesting nutrients and absorbing solutes and electrolytes, the intestinal epithelium with its barrier function is in charge of a tightly controlled antigen trafficking from the intestinal lumen to the submucosa. This trafficking dictates the delicate balance between tolerance and immune response causing inflammation. Loss of barrier function secondary to upregulation of zonulin, the only known physiological modulator of intercellular tight junctions, leads to uncontrolled influx of dietary and microbial antigens. Additional insights on zonulin mechanism of action and the recent appreciation of the role that altered intestinal permeability can play in the development and progression of chronic inflammatory disorders has increased interest of both basic scientists and clinicians on the potential role of zonulin in the pathogenesis of these diseases. This review focuses on the recent research implicating zonulin as a master regulator of intestinal permeability linked to the development of several chronic inflammatory disorders.
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“Zonulin is a protein that participates in the integrity of tight junctions, that is, the maintenance of intestinal integrity.”
From Kefir and Intestinal Microbiota Modulation: Implications in Human Health (2021) · cites this paper as [82]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“In the presence of tight junctions, there is control of the passage of molecules through the paracellular content, which prevents the development of inflammatory processes and the occurrence of diseases.”
From Kefir and Intestinal Microbiota Modulation: Implications in Human Health (2021) · cites this paper as [82]
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“However, the increase in zonulin production leads to loss of function of the intestinal barrier with consequent passage of antigens through the paracellular content and activation of the innate immune response (82).”
From Kefir and Intestinal Microbiota Modulation: Implications in Human Health (2021) · cites this paper as [82]
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“Obesity, which is strongly linked to changes in the gut microbiome, has also been associated with increased intestinal paracellular permeability and endotoxemia114,117.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [117]
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“serum concentrations of zonulin, a protein that increases intestinal permeability, appear to be elevated in obese children and adults117,119, and in persons with type 2 diabetes118, NAFLD, coronary heart disease, polycystic ovary syndrome, autoimmune diseases and cancer117.”
From Chronic inflammation in the etiology of disease across the life span (2019) · cites this paper as [117]
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Khaled, H., Casado‐Carbajo, J., García‐Calvo, X., Hernández‐Rubio, A., López-Casas, J., Leis, A., Morán, T., Zuluaga, P., Muga, R., & Fuster, D. (2026) · Alcohol · doi:10.1016/j.alcohol.2026.107459
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Nekrasova, A. S., Бакулина, Н. В., Elokhina, E. A., Викторович, Т. С., Balakhonova, K. S., Batotsyrenova, C. A., Gasparyan, M. A., Deev, R. V., & Simanenkov, V. I. (2026) · Medical alphabet · doi:10.33667/2078-5631-2026-16-30-38
Metadata
- Authors
- Sturgeon, C., & Fasano, A.
- Affiliations
- University of Maryland, Baltimore (US)
- Massachusetts General Hospital (US)
- Corresponding author
- Fasano, Alessio
- ORCID
- Fasano, Alessio
- Venue
- Tissue Barriers
- Publisher
- Informa UK Limited
- Published
- 2016-10
- Volume
- 4
- Issue
- 4
- Pages
- e1251384
- ISSN
- 2168-8362 (ISSN-L)
- 2168-8370
- PMC
- PMC5214347
- OpenAlex
- W2532623505
- Cited by
- 497
- References
- 155
- Citations by year
- 2026: 42 · 2025: 61 · 2024: 63 · 2023: 70 · 2022: 89 · 2021: 63 · 2020: 52 · 2019: 24 · 2018: 22 · 2017: 11
- FWCI
- 3.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Tissue Barriers (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK048373, R01DK104344)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
- Keywords
- zonulin, intestinal permeability, intestinal barrier function, tight junctions, epithelial barrier function, endothelial barrier, antigen trafficking, immune tolerance, chronic inflammatory diseases, dietary antigens, microbial antigens
- MeSH terms
- Animals, Autoimmune Diseases, Cholera Toxin, Haptoglobins, Humans, Intestinal Mucosa, Protein Precursors, Inflammatory Bowel Diseases, Tight Junctions, Endothelial Cells
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