Gastrointestinal Health Marker Guide

Zonulin

What this marker measures

This marker measures zonulin family peptides, or ZFPs, in stool. ZFPs are proteins detected by the assay that are structurally related to zonulin and may include proteins such as properdin, rather than zonulin itself1. While serum ZFPs have been associated with some conditions linked to altered gut barrier function^2–6, the biological significance of stool ZFPs is less well understood.
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Assay indications

Adapted from the instructions for use

Thezonulinsystem is more activated in coeliac disease and type 1 diabetes mellitus, with elevatedzonulinand anti-zonulinantibodiesobservedin active coeliac disease compared to non-coeliac patients and those in remission on a gluten-free diet. Increased intestinal permeability is associated with the metabolic syndrome, obesity, and several autoimmune, inflammatory, and neoplastic diseases, and has been implicated in conditions including multiple sclerosis, rheumatoid arthritis, asthma, and inflammatory bowel diseases.

Clinical associations*

Consider this marker when your patient presents with:

Stress and lifestyle

Acute psychological stress or high-intensity exercise may be associated with altered intestinal permeability; interpret stool ZFPs cautiously and alongside symptoms and other markers.

Histamine-related context

Elevated stool ZFPs may co-occur with elevated faecal histamine or histamine intolerance features, but evidence is limited and not diagnostic.

Barrier research context

Zonulin-related pathways are involved in tight-junction regulation, but stool ZFPs should not be interpreted as a validated stand-alone measure of gut barrier integrity or intestinal permeability.

*In addition to the assay’s intended use, all clinical associations have been reviewed by the Microba science team to ensure clinical validity supported by Microba’s cited literature.

Interpreting the result

OUT OF RANGE

> 100 ng/ml Elevated stool zonulin family peptides.

The clinical significance of stool ZFPs is still emerging and this result should not be interpreted as a stand-alone marker of increased intestinal permeability. Consider possible contributing contexts such as high-intensity exercise, acute psychological stress, elevated faecal histamine, intestinal inflammation, symptoms, and other relevant markers.

IN RANGE

≤ 100ng/ml Result is within the reference range.

This does not suggest elevated stool ZFPs. Interpret in the context of the patient’s clinical presentation and other gut barrier or inflammatory markers.

CLINICAL NOTE

Zonulin is an acute phase marker.

A single elevated result reflects active stimulation at time of testing. Address stimulating factors for sustained improvement.

Treatment guidance

Address the cause and support intestinal barrier function.

Supplementation

Glutamine supplementation may reduce intestinal permeability in selected populations^7–9.
GRADE C

Zinc carnosine supplementation may reduce intestinal permeability in selected contexts, such as exercise-associated permeability changes^10.
GRADE C

Bovine colostrum supplementation may reduce intestinal permeability in some clinical or exercise-related contexts.1^1–14GRADE C

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Supplementation - proboiotic

Saccharomyces boulardii may reduce intestinal permeability in patients with Crohn’s disease in remission¹⁵.

Tips for discussing out-of-range results

This marker measures zonulin family peptides, involved in regulating your gut barrier. A high result doesn't confirm increased permeability on its own, but it helps guide the conversation alongside your symptoms and other markers

Evidence grading for patient management insights

The letter grades shown next to each patient management insight show the quality of the research behind it. Every insight provided has been through a rigorous review of the scientific literature and graded using the NHMRC Levels of Evidence, so you can see exactly how strong the evidence is before applying it in practice.

Secretory IgA- Reference sourcesSource references for all clinical associations, interpretation definitions, and patient management insights on this card.

1. Scheffler, L. et al. Widely Used Commercial ELISA Does Not Detect Precursor of Haptoglobin2, but Recognizes Properdin as a Potential Second Member of the Zonulin Family. Front. Endocrinol. 9, (2018).
2. ElGhandour, A. M. et al. Value of zonulin as a diagnostic and prognostic marker in different degrees of nonalcoholic fatty liver disease. Egyptian Liver Journal 14, 43 (2024).
3. Arango-González, A. et al. Putative intestinal permeability markers do not correlate with cardiometabolic health and gut microbiota in humans, except for peptides recognized by a widely used zonulin ELISA kit. Nutrition, Metabolism and Cardiovascular Diseases 33, 112–123 (2023).
4. Yuan, J.-H. et al. Impaired intestinal barrier function in type 2 diabetic patients measured by serum LPS, Zonulin, and IFABP. Journal of Diabetes and its Complications35, 107766 (2021).
5. Aasbrenn, M., Lydersen, S. & Farup, P. G. Changes in serum zonulin in individuals with morbid obesity after weight-loss interventions: a prospective cohort study. BMC Endocr Disord 20, 108 (2020).
6. Ohlsson, B., Orho-Melander, M. & Nilsson, P. M. Higher Levels of Serum Zonulin May Rather Be Associated with Increased Risk of Obesity and Hyperlipidemia, Than with Gastrointestinal Symptoms or Disease Manifestations. Int J Mol Sci 18, 582 (2017).
7. Zhou, Q. et al. Randomised placebo-controlled trial of dietary glutamine supplements for postinfectious irritable bowel syndrome. https://doi.org/10.1136/gutjnl-2017-315136 (2019) doi:10.1136/gutjnl-2017-315136.
8. Ried, K., Travica, N., Dorairaj, R. & Sali, A. Herbal formula improves upper and lower gastrointestinal symptoms and gut health in Australian adults with digestive disorders. Nutrition Research 76, 37–51 (2020).
9. Zuhl, M. N. et al. Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression. J Appl Physiol (1985)116, 183–191 (2014).
10. Davison, G., Marchbank, T., March, D. S., Thatcher, R. & Playford, R. J. Zinc carnosine works with bovine colostrum in truncating heavy exercise–induced increase in gut permeability in healthy volunteers12. The American Journal of Clinical Nutrition 104, 526–536 (2016).
11. Hałasa, M., Maciejewska-Markiewicz, D., Baśkiewicz-Hałasa, M., Safranow, K. & Stachowska, E. Post-Delivery Milking Delay Influence on the Effect of Oral Supplementation with Bovine Colostrum as Measured with Intestinal Permeability Test. Medicina (Kaunas) 56, 495 (2020).
12. Hałasa, M. et al. Oral Supplementation with Bovine Colostrum Decreases Intestinal Permeability and Stool Concentrations of Zonulin in Athletes. Nutrients 9, 370 (2017).
13. Marchbank, T. et al. The nutriceutical bovine colostrum truncates the increase in gut permeability caused by heavy exercise in athletes. American Journal of Physiology-Gastrointestinal and Liver Physiology 300, G477–G484 (2011).
14. Buckley, J. D., Butler, R. N., Southcott, E. & Brinkworth, G. D. Bovine Colostrum Supplementation During Running Training Increases Intestinal Permeability. Nutrients 1, 224–234 (2009).
15. Garcia Vilela, E. et al. Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn’s disease in remission. Scand J Gastroenterol 43, 842–848 (2008).