Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases

Sturgeon, Craig; Fasano, Alessio

doi:10.1080/21688370.2016.1251384

Cited by 497Gastrointestinal motility and disordersBarrier Structure and Function StudiesInflammatory Bowel Disease

Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases

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Sturgeon, Craig, Fasano, Alessio·2016·Tissue Barriers

DOI 10.1080/21688370.2016.1251384PMC PMC5214347

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Abstract

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, maintaining intestinal integrity.
“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]
The section “Zonulin as a master regulator of intercellular tight junction in health and disease” identifies zonulin as a protein that regulates epithelial tight junctions. But it reports that zonulin increases intestinal permeability, not that it maintains tight-junction integrity. The “Structure of tight junctions” section attributes maintenance of junction integrity to interactions among junctional proteins, not to zonulin. (LLM, conf=0.85)
Experimental — accuracy not yet measured
In the presence of tight junctions, there is control of the passage of molecules through the paracellular content, preventing the development of inflammatory processes and the occurrence of diseases.
“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]
The Structure of tight junctions section (page unavailable) says tight junctions control the passage of molecules through the paracellular space. But the Role of intestinal permeability in disease section says barrier disruption can contribute to disease and is not sufficient for disease development on its own; it does not establish that tight junctions prevent inflammatory processes or diseases outright. (LLM, conf=0.88)
Experimental — accuracy not yet measured
An 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.
“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]
Obesity, which is strongly linked to changes in the gut microbiome, is associated with increased intestinal paracellular permeability and endotoxemia.
“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]
Serum zonulin concentrations appear elevated in obese children and adults and in persons with type 2 diabetes, NAFLD, coronary heart disease, polycystic ovary syndrome, autoimmune diseases, and cancer.
“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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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
DOI: 10.1080/21688370.2016.1251384
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
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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Zonulin, a regulator of epithelial and endothelial barrier functions, and its involvement in chronic inflammatory diseases

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