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This article explains what zonulin testing is and how it can provide valuable insights for people suffering from a variety of different health concerns.

The term ‘gut health’ has been appearing more frequently in medical news lately, as millions of people struggle with gastrointestinal concerns such as SIBO, IBS, constipation, Crohn’s disease, ulcerative colitis, and celiac disease. 

The good news is that there have been significant advances in the past few years in terms of not only recognizing the signs and symptoms of poor gut health, but also of understanding the root causes and biological foundations of gastrointestinal dysfunction.

Even better yet, we have access to functional medicine laboratory testing that allows for individual assessment of biological markers of intestinal health.

One test that provides valuable insights into intestinal health measures the levels of a protein called zonulin.  This article will go into more detail about what zonulin is, why zonulin levels matter, and who can benefit from laboratory testing for zonulin.

Zonulin Testing Primer: A Gut Health Overview

To properly understand what zonulin is, it’s important to first understand what intestinal health looks like.

The lining of our intestines is made up of a wall of cells held tightly together.  This wall, also known as a mucosal barrier, measures 9m in length and allows for optimal absorption of nutrients during the digestive process.  The barrier is also important because it prevents substances, such as partially digested food, bacteria, and various toxins, from passing (or permeating) out of the small intestine into the bloodstream.   

When the junctures between cells of the mucosal barrier weaken, intestinal permeability increases.  This is known as ‘leaky gut.’ 

Normally, fluids, electrolytes, and small food particles are able to pass through the mucosal lining.  However, when leaky gut develops, toxins, pathogens, and large food particles can also permeate the gut barrier.  The body then recognizes these substances as foreign invaders, and this triggers an inflammatory immune response. 

Zonulin Testing, Gut Health, and Chronic Disease

Leaky gut has been linked with several gastrointestinal conditions including IBS, celiac disease, ulcerative colitis, and Crohn’s disease.  Some members of the scientific community suggest that the inflammatory response triggered by leaky gut is also responsible for non-gastrointestinal conditions such as fibromyalgia, asthma, chronic fatigue syndrome, arthritis, and some autoimmune conditions like multiple sclerosis and rheumatoid arthritis.    

Zonulin is a protein that regulates intestinal permeability.  When it is released, it makes the gaps between cells of the intestinal lining bigger, allowing larger molecules to pass through the lining into the bloodstream.  Therefore, elevated zonulin is correlated with leaky gut syndrome and its associated inflammatory and autoimmune disorders (1).  This is confirmed by the fact that people with autoimmune disorders such as celiac disease tend to have excess levels of zonulin in their blood.  Research has also shown that up-regulation of zonulin is tied to hyperglycemia in pre-diabetic patients (2).   

Finally, zonulin’s role in aggravating intestinal permeability is also relevant to individuals with histamine intolerance.  This is because gut permeability can contribute to DAO deficiency, which in turn allows excess histamine to build up in the body (3).  You can learn more about the relationship between gut health and histamine intolerance here

What Causes Excess Zonulin Release?

The gastrointestinal tract contains trillions of bacteria, represented by over 5,000 different strains arranged in various collections, or colonies.  When these bacterial colonies are out of balance, the gut is said to be in a state of dysbiosis.  This can be the result of a lack of diversity in your microbiota, or an unusually high or low occurrence of certain types of bacteria.

Various factors that can contribute toward dysbiosis include dietary changes, medications (particularly antibiotics), high alcohol consumption, and chemicals and toxins in food and your external environment. 

Regardless of the cause, gut dysbiosis results in an increased production of zonulin (4).

Some research suggests that the body increases zonulin levels in response to certain species of bacteria as a defensive mechanism, or a way of flushing out foreign microorganisms from the small intestine (5). 

One component of gluten, known as gliadin, may also activate the release of zonulin. This is an important finding for celiac patients: their intolerance to gluten leads to a consistently high level of zonulin, which in turn will compromise the lining of the gut and provoke chronic inflammation in the body.

Fortunately, zonulin has a reversible impact on intestinal permeability.  Once the triggers are addressed, zonulin levels decrease and gut barrier function is restored.    

What Can Be Done to Address Elevated Zonulin Levels?

As mentioned above, the negative effects of elevated zonulin levels can be reversed by adopting a diet and lifestyle that promote the health and integrity of the mucosal barrier. 

Dietary changes that restore gut health include:

• Avoiding the ‘Standard American Diet’ which is high in processed foods, refined grains, sugar, and saturated fat.

• Reading nutrition labels and looking out for preservatives and artificial colors, flavors, and sweeteners.

• Increasing fiber intake; this nutrient is critical for establishing healthy gut flora.

• Aiming for 8-10 servings of fruits and vegetables daily to ensure you’re getting the variety of nutrients necessary to maintain a diversity of bacteria in your gut. 

Lifestyle recommendations for gut health include regular physical activity and hydration, adequate sleep, and a consistent stress management practice.  More detailed recommendations can be found in this article about keeping your gut microbiome healthy during COVID-19.   

It is also a good idea to limit exposure to environmental toxins as much as possible; more is explained in this article

Who Should Consider Zonulin Testing?

People with chronic illnesses associated with leaky gut should consider zonulin testing.  This includes individuals with gastrointestinal concerns, as well as those who have been diagnosed with:

• Celiac disease

• Non-celiac gluten sensitivity

• Crohn’s disease

• Irritable Bowel Syndrome (IBS)

• Inflammatory Bowel Disease (IBD

• Type 1 Diabetes

• Multiple Sclerosis

• Rheumatoid Arthritis

In addition, research will show leaky gut to be associated with a variety of conditions and organs that involve “-itis” or inflammation, so zonulin in a functional medicine practice can be an important assessment tool. For the lungs, in bronchitis or asthma. For the skin, dermatitis or eczema. And then there is this axiom: leaky gut, leaky brain – associating the gut lining/barrier with the blood-brain barrier.

Testing for elevated zonulin levels is the key first step to addressing these health concerns, because the test can confirm whether gut permeability is a contributing factor in your symptoms or diagnosis.  Once leaky gut is established as an underlying issue, steps can be taken to address it and restore a state of balance in the microbiome. 

How is Zonulin Testing Performed?

Levels of zonulin (and its related family of peptides) are measured using a laboratory test designed to assess intestinal permeability.  The test is based on a dried blood spot collected at home with a testing kit.  Contact our clinic here to find out more information and to discuss whether zonulin testing is right for you.

For more personalized guidance, request a functional medicine consultation with Dr. John Gannage, MD

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