Permeability: Zonulin Family Peptides (Zonulin FP)

FLUIDS iQ®’s test for intestinal permeability (“Leaky Gut”), measuring Zonulin and its closely related family of peptides (Zonulin FP), is a cornerstone of our Intestinal iQ™ series of wellness tests. “Leaky Gut” occurs when the gut lining becomes abnormally permeable, allowing bacteria, food and other large molecules to pass through. A major controller of this gateway is Zonulin FP.


What is Zonulin?


Zonulin (pre-Haptoglobin 2) is a protein that modulates the permeability of tight junctions between cells of the digestive tract wall. Zonulin and its related family of peptides, are found within intestinal cells, with production and release, mimicking the effect of certain bacterial toxins. Once triggered, Zonulin plays an important role in the creation of bowel “leakiness.” By a quirk of nature, the wheat glycoprotein, gliadin, mimics the effects of foreign bacteria and also activates Zonulin signaling, irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules. But unlike the effect caused by bacteria, the Zonulin effect from gliadin generates a two-way response. Not only can water exit, but intestinal contents are able to gain entry in the opposite direction, ie: into the bloodstream.

The gliadin-Zonulin leak effect occurs not just in people with celiac disease or gluten-sensitivity; it occurs in everyone. However, the effect is longer and more pronounced (5-fold greater) in the intestinal cells of people with celiac disease.


Sample FLUIDS iQ® Zonulin test report (optimized for Internet Explorer, Firefox and Safari)



Zonulin and recent scientific literature pertaining to intestinal permeability:


• "Zonulin Regulates Intestinal Permeability and Facilitates Enteric Bacteria Permeation in Coronary Artery Disease"


•"Intestinal Permeability and its Regulation by Zonulin Diagnostic and Therapeutic Implications"


"Gut Microbiota, Microinflammation, Metabolic Profile, and Zonulin Concentration in Obese and Normal Weight Subjects"


"Changes in intestinal tight junction permeability associated with industrial food additives explain the rising incidence of autoimmune disease"


• "Systemic autoimmune disorders in celiac disease"


• "Diagnosis and Treatment of Celiac Disease"


• "Mechanisms of Disease: the role of intestinal barrier function in the pathogenesis of

gastrointestinal autoimmune diseases"


• "Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer"


• "Increased Intestinal Permeability Correlates with Sigmoid Mucosa alpha-Synuclein Staining and Endotoxin Exposure Markers in Early Parkinson’s Disease"


• "The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease"


• "Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms"


• "Circulating endotoxin and systemic immune activation in sporadic Amyotrophic Lateral Sclerosis (sALS)"


"Zonulin upregulation associated with increased gut permeability in subjects with Type 1 Diabetes and their relatives"


"Circulating increased in association with obesity-associated insulin resistance"


"Inulin-enriched pasta improves intestinal permeability and modifies the circulating levels of Zonulin and glucagon-like peptide 2 in healthy young volunteers" 


• "New markers of insulin resistance in polycystic ovary syndrome"


"Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation"