• Jasmine Blake Hollywood, MS, HHP

What is Zonulin? How Gluten affects your Body

Updated: Sep 18, 2020

The Wheat Allergy

If food is cross-contacted, a person with a wheat allergy could suffer greatly. A wheat allergy is an allergic reaction caused by an IgE mediated immune response to a particular food. This allergy is not the same as celiac or gluten sensitivity. IgE means if a person has a wheat allergy, they will experience a life-threatening reaction such as anaphylactic shock.

Anaphylactic shock can result in the closing of the throat or tongue, swelling under the skin, hives, rashes, or even swelling of the eyes or face. A person with an IgE mediated allergy can also experience fainting, lightheadedness, low blood pressure, dizziness, difficulty breathing, rapid breathing, shortness of breath, nausea or vomiting, or mental confusion. If a person has a wheat allergy, they can eat any grain with or without gluten except wheat grains, and this must be avoided their whole life. [3]. Essentially, a person with a wheat allergy does not have a gluten allergy.

Gluten Sensitivity

Food Sensitivity testing assesses IgG allergies and gluten sensitivity (food intolerance) is not an IgE mediated allergy. [3]. Gluten intolerance is when a person eats a particular food, such as gluten, and they feel a certain way afterward. Also, the gluten may cause an issue in the body after consuming for an extended period. People who are intolerant against gluten do NOT get life-threatening symptoms. If a person has a gluten sensitivity, gluten should be avoided for at least six months. [3]. If the gut can heal the person may be able to add it back in. [3]. Sometimes with a food sensitivity such as gluten, the food cannot be added back in.

Symptoms of gluten sensitivity are:

  • Headache

  • Bloating

  • Constipation

  • Abdominal discomfort

  • Diarrhea

  • Food craving

  • Fatigue

  • Difficulty in concentration

  • Mood Swings

  • Hyperactivity

  • Joint/Muscle pain

Celiac Disease

In celiacs, the gut lining is attacked by the immune system during a chronic autoimmune attack due to the individual ingesting gluten. [3]. People with celiacs cannot break down gluten. Gluten causes the gut barrier to break apart. People with celiac disease acquire a condition called intestinal permeability.

Intestinal permeability is when the gut barrier breaks down so much that things ingested can pass through the lining of the gut wall. Another name used for intestinal permeability is leaky gut. When passing through the gut barrier, food particles can enter into the bloodstream; ultimately "leaking from the gut" to the blood. Some of these particles are larger than usual.

When the large particles are in the bloodstream, the body does not understand what they are. This reason is that they are not supposed to be there. So the body thinks these large particles are invaders. Eventually, the gut continues to deteriorate as more gluten is eaten.

What are Tight Junctions?

The gut lining is like a fence that spreads across the gastrointestinal wall. Just like a fence, it has links that are tied together. These are called tight junctions. Tight junctions are in place so that the fence or barrier does not break and things cannot get through that are not supposed to. When thinking of a fence, only things small enough to get the wholes can pass. The purpose of the gut wall is to keep certain things out like pathogens, food particles, or bacteria; while letting in the smaller molecules like nutrients and other things that the body can utilize.

What is Zonulin and How does Gluten affect your Body?

Since gluten is associated with leaky gut, it is good to understand what gluten does to the gut lining. Inside the gut lining where the tight junctions are located, there is zonulin. Zonulin is the particular protein produced by the body that keeps the gut lining permeable. In other words, it keeps the fence links from breaking.

In people, who react to gluten, the interaction between the gliadin protein and the gut wall increases the release of the zonulin protein. [9]. Gliadin is a class of proteins found in wheat. As zonulin is released, it is attracted to the wall where the gliadin is located. Here it binds to the wall surface. As it binds, this process reduces resistance at the tight junctions. [6].

Zonula occludens toxin (ZOT) is a chemical that is released by Vibrio cholerae. Vibrio cholerae is a bacteria in the gut. [1]. The resistance that occurs at the tight junctions when zonulin leaves is affected because of ZOT. How the resistance is affected is because ZOT and zonulin compete to bind to the same cell receptors.

These receptors are located at the tight junctions. [1]. Because zonulin competes with binding to the receptors, zonulin will usually keep ZOT from breaking down the tight junctions of the gut lining. As zonulin is released due to the constant ingestion of gliadin, to bind to the wall surface, it leaves tight junctions vulnerable. Consequently, there is a loss of ZOT interaction. [9]. The ZOT chemical then begins to inflame the tight junctions. [1].

As a person continues to eat gluten-containing foods, these chemicals are continuously released. The continual release of ZOT eventually causes tight junctions to loosen and break. This process results in a leakage of the lining. [1]. In other words, after lots of rain, the fence begins to corrode, and the links on the fence start breaking; allowing what is on the other side of the fence to enter. This process is also known as leaky gut.

How to Test for Celiac Disease Antibodies

When testing for Celiac disease, the practitioner is looking at specific types of elevated autoantibodies. Autoantibodies are antibodies sent out by the body's immune system to fight ongoing issues. Particularly in celiacs, the anti-tissue transglutaminase (anti-tTG) antibody, also known as the IgA marker, will be elevated. [7].

Another antibody that will be elevated is the antiendomysial antibody (EMA). [7]. This antibody is known as another IgA marker or autoimmune (anti "self") marker. [7]. Also, the deaminated gliadin peptide (DGP), also known as the IgG and IgA markers or anti-gluten markers, will be elevated. [7].

Practitioners can also combine HLA typing with EMA and DGP tests when testing for celiacs. They can also test for the gene types HLA DQ2, which is almost 100% found in celiac patients, as well as HLA DQ8. [2]. HLA stands for human leukocyte antigen. [2]. HLAs are gene encoders responsible for the regulation of the immune system. [2].

People with celiacs have a significant level of HLA DQ2 complex and significant elevation of antibody types present in blood work. [2]. This high elevation of antibodies is due to all the large particles getting in through the stomach lining into the bloodstream.

Other diagnostic tools that can suggest celiacs disease are to:

  • assess malnutrition

  • test for iron-deficient anemia (which is common in most celiacs patients)

  • test for micronutrient deficits (particularly Selenium, B9/B12, and Zinc), which point to gut lining destruction because the gut cant absorb properly because it is inflamed from all the damage and focused on repairing itself

  • test for lymphocytic enteritis

  • asses for signs of diarrhea (which is common in celiacs patients); and

  • test for osteoporosis.

How to Test for Gluten Sensitivity

Gluten sensitivity has similar leaky gut damage without the injury of the gut lining. However, symptoms are similar to that of celiacs. People who are gluten sensitive can also have the same vitamin and mineral deficiencies as people with celiacs. Therefore, using micronutrient testing is an excellent tool to assess micronutrient percentages. [3]. Many individuals with gluten sensitivity will have the same elevated DGP IgG marker on their labs, but not the IgA marker. (Pizzorno et al., 2016). Other sources that can help differentiate from celiac disease are using food sensitivity tests.

Examples of companies that offer gluten sensitivity tests are:


  • Genova Diagnostics

  • Doctors Data, and

  • Lab Corp

Sensitivity to gluten can cause other autoimmune diseases as well. So an excellent diagnostic tool would be to test for other elevated antibodies that are found in common autoimmune diseases. Additionally, constipation is common in those who have gluten sensitivity.[2].

Most people who suffer from gluten sensitivity and celiac disease will have some form of gut issues. These people will have some extent of Hypochlorhydria (low stomach acid). Also, some will associate their symptoms with low pancreas enzymes or low bile acid production. These symptoms are due to gallbladder dysfunction. As well, some people often are diagnosed with other diseases such as thyroid disease, neurological disorders, liver issues, irritable bowel syndrome, or other gastrointestinal issues. [2].


  1. Di Pierro, M., Lu, R., Uzzau, S., Wang, W., Margaretten, K., Pazzani, C., Maimone, F., et al. (2001). Zonula occludens toxin structure-function analysis: Identification of the fragment biology active on tight junctions and of the zonulin receptor binding domain. The Journal of Biological Chemistry, 276, 19160-19165. doi: 10.1074/jbc.M009674200

  2. Gaby, A. R. (2017). Nutritional medicine, (2nd Ed.). Concord, NH: Fritz Perlberg Publishing.

  3. Gluten Sensitivities. (2017). Medicine Plus. Department of Health and Human Services: Office on Women's Health. Retrieved from https://medlineplus.gov/glutensensitivity.html

  4. Kneesi, R. (2019). NUTR635, Module 7 [Resources]. Retrieved from Lecture Notes Online Web site https://www.muih.edu

  5. Mahan, L. K. & Raymond, J. L. (2017). Krause’s food and the nutrition care process (14th Ed.) St. Louis MO: Elsevier

  6. Nehra, V., Marietta, E. V., & Murray, J. A. (2014). Celiac disease and its therapy: Current approaches and new advances, (Chpt 12). In Wheat and Rice in Disease Prevention and Health: Benefits, Risks and Mechanisms of Whole Grains in Health Promotion, pages 143-155. https://doi.org/10.1016/B978-0-12-401716-0.00012-X

  7. Pizzorno, J., Murray, M., & Joiner-Bey, H. (2016). The clinician’s handbook of natural medicine, (3rd Ed.).St. Louis, MO: Elsevier.

  8. Ross, C. A., Caballero, B., Cousins, R. J., Tucker, K. L., & Ziegler, T. R., (2014). Modern nutrition in health and disease (11th Ed.). PA: Wolters Kluwer.

  9. Visser, J., Rozing, J., Sapone, A., Lammers, K., & Fasano, A. (2009). Tight junctions, intestinal permeability, and autoimmunity: Celiac disease and type 1 diabetes paradigms. Annals of the New York Academy of Sciences1165, 195–205. doi:10.1111/j.1749-6632.2009.04037.x

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