Zonulin's Role In Gut Health

The intestinal lining in the digestive tract is a thin, single-cell layer, and this delicate barrier is the largest and most important barrier against the external environment! Just a decade or two ago, discussing intestinal barrier permeability was ridiculed, but today it is widely recognized in the scientific literature as a very real biological phenomenon. Disrupted intestinal barrier function, or leaky gut, is associated with a long list of chronic inflammatory conditions including autoimmune disease, food allergy, inflammatory bowel disease, celiac disease, eczema, psoriasis and autism.

Intestinal Barrier, Tight Junctions and Leaky Gut

The delicate intestinal lining in your gut consists of tightly joined cells. Where these cells join together to form a barrier is called a tight junction, which opens and closes as needed. Tight junctions allow for absorption of nutrients from the food we eat, while at the same time, protect against the entry of allergens, bacteria, fungi, and parasites. Tight junctions act like a gatekeeper, but when they malfunction, “stuff” makes it into the bloodstream that shouldn’t. This loss of intestinal barrier function is called “leaky gut” and can lead to allergies and autoimmune disorders (1). If you suspect you have leaky gut, here are 4 proven steps to put a stop to it. 

What is Zonulin?

In 2000, researcher Alessio Fasano and his team discovered zonulin, a damaging protein produced in the gut that alters the permeability of the tight junctions in the digestive tract. Zonulin production induces an increase in intestinal permeability.

In healthy cells, if zonulin is secreted, cells open and then close. However, in people with serious health conditions, particularly autoimmunity, circulating zonulin is like pressing and holding the open button on the remote. There’s so much zonulin produced, therefore, the tight junctions get stuck open.

Dysbiosis, Leaky Gut, and Zonulin

A healthy balance of microbial flora in the gut is essential for intestinal health. When its fragile balance is altered, it’s called dysbiosis. Dysbiosis is one of the key factors that causes zonulin release and subsequent loss of intestinal barrier function. Zonulin is the remote control that opens the tight junctions between cells (1).  

When there are alterations of the gut wall permeability, this increases antigen traffic through the gut wall to the bloodstream, triggering an immune response. Many things can lead to dysbiosis, including exposure to antibiotics, chronic stress, nutrition choices, food intolerance, and pesticides like glyphosate (just to name a few).

Improving your gut health is super important for overall health, and starting with your diet is key. Your gut will love these five foods, along with some of my favorite gut nourishers. Those good bugs feed off prebiotics, which come from fresh fruits and vegetables, so try out my favorite green drink recipe to help out the good bugs in your gut. 

Zonulin Linked to Numerous Chronic Health Conditions

Elevated zonulin levels have been found in people with autism, depression, type 1 diabetes, type 2 diabetes, metabolic syndrome, and PCOS. It’s also associated with systemic inflammation and is particularly elevated in those with celiac disease (2).

Zonulin and Gluten

Gliadin, a protein found in wheat, is a potent stimulator of zonulin release (3). If you’re eating a number of foods that create an immunologic response, including gluten, you will have greater levels of systemic inflammation.  

Testing for Zonulin

Testing serum zonulin levels in order to assess intestinal barrier dysfunction sounds like a good idea; however, the current commercial assays have significant methodological inconsistencies and serum zonulin isn’t a reliable marker at this time (4). With time, I'm confident zonulin will become a dependable marker for gut health. 

Kelly Harrington, MS, RDN

Registered Dietitian Nutritionist for Healthy Goods



1. Groschwitz K and Hogan S. Intestinal Barrier Function: Molecular Regulation and Disease Pathogenesis. J Allergy Clin Immunol. 2009 Jul; 124(1): 3–22.  

2. Fasano A. Zonulin, a newly discovered modulator of intestinal permeability, and its expression in coeliac disease. Lancet. 2000 Apr 29;355(9214):1518-9.

3. Drago S et al. Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines. Scand J Gastroenterol. 2006 Apr;41(4):408-19.   

4. Ajamian M et al. Serum zonulin as a marker of intestinal mucosal berrier function: May not be what it seems. Published online 2019 Jan 14.

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