Zonulin Testing

Zonulin "unlocks" the intestinal barrier and creates a leaky gut

What is Zonulin?

Zonulin is a protein biomarker and regulator of gastrointestinal tight gap junctions that "unlocks" the intestinal barrier and creates a leaky gut, allowing large peptides to cross the lining into the bloodstream, leading to systematic inflammation of the body.

Research and clinical studies of the protein zonulin and the zonulin signaling pathway demonstrate the clinical efficacy of zonulin as a biomarker of intestinal permeability. Studies also confirm that zonulin signaling is an essential mechanism in promoting healthy immune function and tolerance at the gastrointestinal mucosal barrier.

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 a leaky gut develops, toxins, pathogens, and large food particles can also permeate the gut barrier.  The body then recognizes these substances as foreign invaders, triggering 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 scientific community members suggest that the inflammatory response triggered by a leaky gut is also responsible for non-gastrointestinal conditions such as fibromyalgia, asthma, chronic fatigue syndrome, arthritis, and some autoimmune diseases like multiple sclerosis and rheumatoid arthritis.

Zonulin is a protein that regulates intestinal permeability.  When released, it makes the gaps between intestinal lining cells 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. 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 the up-regulation of zonulin is tied to hyperglycemia in pre-diabetic patients.

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, allowing excess histamine to build up in the body.

What Causes Excess Zonulin Release?

The gastrointestinal tract contains trillions of bacteria, represented by over 5,000 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 result from a lack of diversity in your microbiota or an unusually high or low occurrence of certain types of bacteria.

Various factors contributing to 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.

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.

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 will compromise the gut lining and provoke chronic inflammation.

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 adverse effects of elevated zonulin levels can be reversed by adopting a diet and lifestyle promoting the mucosal barrier's health and integrity.

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 for preservatives, artificial colors, flavors, and sweeteners.

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

• Aim 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.

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 various 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 contributes to your symptoms or diagnosis.  Once a leaky gut is established as an underlying issue, steps can be taken to address it and restore a state of balance in the microbiome.


Scroll to Top
Skip to content