Elevated Zonulin: Tight Junctions, Leaky Gut and Autoimmune Disorders: What is the Connection?

What is Zonulin

Zonulin is a protein that that controls the opening and closing of the tight junctions in the gut. In a healthy gut, the small space in between the tight junctions is used to transport nutrients back and forth. When the tight junctions are wide open, this causes an increase in paracellular permeability (lining between the gut and blood stream), inducing what we call ‘leaky gut’ syndrome. The increase in paracellular permeability allows toxins and undigested food particles from the gut and slip into the blood stream. This can stimulate an autoimmune reaction in the body.

Having a leaky gut may be harmful to your health because it allows waste and toxins such as undigested food particles, bacteria and fungi to spread throughout your body, leading to inflammatory processes, immune disorders and food reactions.

Zonulin plays a major role as a regulator of intestinal barrier function. Elevated levels of zonulin are a biological door to inflammation, autoimmunity and yes, certain types of cancer have been associated with elevated levels of zonulin.

Zonulin was discovered in 2000 by Alessio Fasano, is a protein secreted by the cells in the gut wall that stimulate the opening of gaps between cells in the intestinal barrier. Zonulin has been implicated in the pathogenesis of several disease processes such as celiac disease, diabetes mellitus type 1 and Type 2 diabetes. Those who suffer from these diseases have shown increased levels of zonulin and an increase in intestinal permeability because zonulin causes a breakdown of the tight intracellular junctions between the epithelial cells of the gut wall. Of note, research has shown the effects of zonulin are reversable.

Symptoms Associated with Leaky Gut Syndrome

Leaky gut syndrome has been linked to myriad of health issues that have a direct affect on the gut (or is it the other way around). Joint pain, rosacea, eczema, anxiety and hormon imbalances have been associate with leaky gut syndrome.

Some GI Indicators of Leaky Gut Syndrome May Be, But Not Limited to:

• Painful indigestion – GERD
• Diarrhea
• Bloating
• Gassy

What are Tight Junctions

The paracellular (Paracellular transport is the transport of ions and molecules) that occurs in between cells, passing through an intercellular pathway. Tight junctions are found between the intestinal epithelial cells and play a crucial role creating a protective mucosal barrier in the gut while regulating the functional condition of the paracellular pathway.
The tight junction (TJ) create a protective barrier for both the passage of ions and molecules through the paracellular pathway. Basically, tight junctions are the gate keepers from letting molecules slip in between epithelial cells in the gut.

Zonulin and the Immune System

We know that 70 – 80% of immune system is in the GI tract. When any part of the body experiences trauma or injury, our bodies shift into protect mode. It has been estimated, that within a few hours of injury, bacteria from the gut migrates from the bowel into the lamina propria (The lamina propria is made up of structural protein molecules, nerves and veins. The lamina propria carries blood supply to the epithelium)of the intestine and the lymphatic system and other organs. Could this process be an adaptive part of our immune system? Think about this……. When an animal gets injured, the animal will lick the wound or injury and will swallow the bacteria that can be found within the injury . These bacteria will be quickly shunted to the immune system so it can identify the bacteria to help fight the infection.

Leaky gut wreaks havoc in the body, weakening immunity and causing widespread problems. What happens in GI track doesn’t just stay in the gut. In the case of leaky gut, molecules and protein particles escape the GI track and invade the circulatory system. This process happens over and over again, stimulating an immune response which leads to autoimmune and inflammatory disorders. Leaky gut and lead to chronic or recurring infections.

Where Are Immune Cells Located in the gut?

The central part of the villus comprises the lamina propria (The lamina propria is made up of structural protein molecules, nerves and veins). The lamina propria carries blood supply to the epithelium, where the majority of intestinal immune cells are found, whereas intraepithelial lymphocytes (IELs) are found lying between epithelial cells in the gut.

What Elevated Levels of Zonulin Could Signify

Elevated levels of zonulin are associated with increased intestinal permeability (Leaky Gut)  because it induces breakdown of the tight intercellular junctions between epithelial cells and toxins can slip from the gut into the blood stream inducing all kinds of health issues, such as various Crohn’s Disease,  Cancers, SIBO, Diabetes, and other inflammatory processes.

Factors That Can Stimulate an Increase in Zonulin

• Nutrients: glucose, amino acids, mid- chain free fatty acids, oligosaccharides

• Bacterial Toxins: Cholera, Clostridium, Lipopolysaccharides

• Infections: Campylobacter, Rotavirus, Giardia

• Stress Hormone: Corticotropin- Releasing Hormone (CRH)

• Cytokines: Tumor Necrosis Factor-Alpha, Interferon – y, IL4.

• Medications: Aspirin, Non-Steroidal Anti-inflammatory medications

• Irritants / Toxics: Alcohol, Carrageen, Dextrin Sulfate

• Food Toxins: lectins, potatoes, eggplant, gliadin fragments, wheat, dairy
products, legumes, nuts, and seeds

• Injury: Burns to the skin, heart failure, fracture

• Nutritional Deficiency’s: Vitamin A, Zinc

• Young Age: Infants, especially premature infants

• Mast Cell Degranulation: tryptase, immune modulators, cytokines, histamine

• Disrupted Sleep: Increase in CHR alters gut motility leading to SIBO

• Oxidative Stress: Damages Mucosa

What You Can Do If You Have Elevated Levels of Zonulin

This may sound simple, and it basically is. You can avoid foods that are known triggers of zoulin such as grains such as wheat, dairy products, legumes, nuts, and seeds. Other known dietary triggers are processed foods and white sugar.

As always, discuss your concerns with your health care provider.

How Can You Find Out What Your Zonulin Levels Are

Always discuss your concerns with your health care provider to find out what steps you need to take to find out what your zonulin levels are.

You can also order your own test for zonulin through MyLabsForLife.com.
It is a simple process. Order your own test kit, it will be mailed directly to you.
Collect your sample and return your test kit to the lab.
It takes approximately two weeks for samples to finalize. Results will be emailed directly to you.

Click on this link to order your own zonulin test or the GI Map with zonulin.

The information provided in this blog is intended solely for informational and educational purposes. It should not be considered medical advice, diagnosis, or treatment. Please discuss specific health conditions and concerns with your health care professional.

Thank you for reading! Your path to enhanced cellular wellness starts here.

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