Add-On: Zonulin

This is a single-marker test measuring zonulin. It is available as an add-on to the GI Effects® profiles. 

What is the Add-On: Zonulin Test by Genova Diagnostics?

This stool test assesses for zonulin in the stool, which indicates intestinal inflammation and a leaky gut presentation.

What is the Clinical Relevance of the Add-On: Zonulin by Genova Diagnostics?  

Assessing zonulin levels through a stool test holds significant clinical relevance, particularly in the context of gastrointestinal health and body-wide conditions related to intestinal permeability. 

Zonulin is a protein that reinforces the tight junctions between intestinal epithelial cells. Elevated levels of zonulin indicate increased intestinal permeability, often referred to as "leaky gut syndrome." 

This happens when intestinal inflammation, commonly caused by intestinal dysbiosis and gluten sensitivity, causes the enterocytes to swell: this weakens tight junctions and allows zonulin to spill into the intestinal lumen. 

Research suggests that elevated zonulin levels may be associated with various gastrointestinal disorders, autoimmune diseases, and metabolic conditions. By measuring zonulin levels in stool, healthcare providers can gain valuable insights into the integrity of the intestinal barrier and identify potential underlying factors contributing to gastrointestinal dysfunction and systemic inflammation.  [5.]

Who Can Benefit from the Add-On: Zonulin by Genova Diagnostics?

Individuals Seeking to Optimize Health: even in the absence of symptoms, this test can offer insights into gut health, providing an opportunity for preventative measures against potential health issues and supporting the body’s natural processes.

Patients with Chronic Digestive Dysfunction: for those who have suffered from chronic symptoms with or without a clear diagnosis, the Add-On: Zonulin by Genova Diagnostics can help identify underlying food sensitivities or inflammation in the gut that may be contributing to their health issues.

Autoimmune Diseases: since gut health is closely linked to the immune system, identifying and addressing compromised gut barrier health can provide additional treatment options and provide crucial support in managing autoimmune conditions. [1., 7.]

Gastrointestinal Disorders: for patients struggling with Small Intestinal Bowel Overgrowth (SIBO), Irritable Bowel Syndrome (IBS) and Inflammatory Bowel Disease (IBD), this test can identify previously silent leaky gut that may be contributing to symptoms like gas, bloating, diarrhea, and constipation. [2., 8.]

Digestive Complaints: people experiencing unexplained digestive issues such as gas, bloating, heartburn, indigestion, diarrhea, or constipation can identify potential causes like leaky gut and receive targeted treatment recommendations.  [8.] 

Neurological and Cognitive Issues: the vagus nerve is the primary nerve that innervates the digestive tract, and is considered the “highway of the gut-brain axis”.  Insights into the gut-brain axis through this Zonulin test may reveal how leaky gut impacts an individual’s cognitive function and affects memory, concentration, and brain fog. [3., 4.]

Skin Conditions: conditions like acne and psoriasis have been linked to gut health. Identifying and addressing leaky gut can be a part of a comprehensive treatment plan to improve and restore skin health. [6.]

Mood Disorders: the gut-brain connection means that digestive inflammation can impact mood and emotional well-being, making this test a valuable assessment tool for individuals with these conditions. [3., 4.]

Additional Resources for Practitioners:

Video: Interpreting the GI Effects Profile 

Article: Using the GI Effects Test in Clinic

References

[1.] Brady DM. Molecular Mimicry, the Hygiene Hypothesis, Stealth Infections and Other Examples of Disconnect between Medical Research and the Practice of Clinical Medicine in Autoimmune Disease. Open Journal of Rheumatology and Autoimmune Diseases. 2013;03(01):33-39. doi:https://doi.org/10.4236/ojra.2013.31007 

[2.] Capobianco I, Di Vincenzo F, Puca P, Becherucci G, Mentella MC, Petito V, Scaldaferri F. Adverse Food Reactions in Inflammatory Bowel Disease: State of the Art and Future Perspectives. Nutrients. 2024 Jan 25;16(3):351. doi: 10.3390/nu16030351. PMID: 38337636; PMCID: PMC10857040. 

[3.] Fasano A. Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer. Physiological Reviews. 2011;91(1):151-175. doi:https://doi.org/10.1152/physrev.00003.2008

[4.] Fasano A. All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases. F1000Res. 2020 Jan 31;9:F1000 Faculty Rev-69. doi: 10.12688/f1000research.20510.1. PMID: 32051759; PMCID: PMC6996528. 

[5.] Hu S, Ding Q, Zhang W, Kang M, Ma J, Zhao L. Gut microbial beta-glucuronidase: a vital regulator in female estrogen metabolism. Gut Microbes. 2023 Jan-Dec;15(1):2236749. doi: 10.1080/19490976.2023.2236749. PMID: 37559394; PMCID: PMC10416750.

[6.] Katta R, Schlichte M. Diet and dermatitis: food triggers. J Clin Aesthet Dermatol. 2014 Mar;7(3):30-6. PMID: 24688624; PMCID: PMC3970830. 

[7.] Paray BA, Albeshr MF, Jan AT, Rather IA. Leaky Gut and Autoimmunity: An Intricate Balance in Individuals Health and the Diseased State. Int J Mol Sci. 2020 Dec 21;21(24):9770. doi: 10.3390/ijms21249770. PMID: 33371435; PMCID: PMC7767453.

[8.] Pasta A, Formisano E, Calabrese F, Plaz Torres MC, Bodini G, Marabotto E, Pisciotta L, Giannini EG, Furnari M. Food Intolerances, Food Allergies and IBS: Lights and Shadows. Nutrients. 2024 Jan 16;16(2):265. doi: 10.3390/nu16020265. PMID: 38257158; PMCID: PMC10821155. 

[9.] Simeonova D, Ivanovska M, Murdjeva M, Carvalho AF, Maes M. Recognizing the Leaky Gut as a Trans-diagnostic Target for Neuroimmune Disorders Using Clinical Chemistry and Molecular Immunology Assays. Curr Top Med Chem. 2018;18(19):1641-1655. doi: 10.2174/1568026618666181115100610. PMID: 30430944.