So what is Zonulin all about?


This month’s article comes from Gut 2001;49:159-162 doi:10.1136/gut.49.2.159

Title: Intestinal zonulin: open sesame!

Author: A Fasano

Hey guys, I was watching a medical talk last week and the doctor was discussing how leaky gut is becoming more prevalent in our society. It is leading to many challenges for patients and that this is new to doctors because although scientists have made several breakthroughs in identifying molecules like zonulin there is much to be learned. It was more than half-way through his talk, that the doctor realized he needed to back-track a bit because many of the doctors in the room were unaware of how zonulin works and I thought wow. Sure I’ve heard of zonulin and understand the basics but it is quite complex so that inspired me to locate an older article explaining some of the basics of zonulin and over the next few months we’ll dive in deeper so that we all have a better understanding how to heal our bodies.

Some may ask why leaky gut is important to understand if you have celiac disease or are non-celiac gluten sensitivity and the truth is for celiacs it is a common complication and health issue that comes up when your body is not healing properly.

I will reference a few key points from the article and then add my thoughts and spin on how it relates to our community below

  • A century ago, TJs (tight junctions) were conceptualized as a secreted extracellular cement forming an absolute and unregulated barrier within the paracellular space. 
  • Biological studies of the past several decades have shown that TJs are dynamic structures subjected to structural changes that dictate their functional status under a variety of developmental, physiological, and pathological circumstances.
  • To meet the many diverse physiological challenges to which the epithelial and endothelial barriers are subjected, TJs must be capable of rapid and coordinated responses. This requires the presence of a complex regulatory system that orchestrates the state of assembly of the TJ multiprotein network.
  • The physiological role of the zonulin system remains to be established but it is likely that this system is involved in several functions, including TJ regulation responsible for the movement of fluid, macromolecules, and leucocytes between the bloodstream and the intestinal lumen and vice versa.
  • It has recently been reported that untreated CD predisposes to autoimmune disorders such as insulin dependent diabetes mellitus, Hashimoto's thyroiditis, autoimmune hepatitis, and connective tissue diseases. One could hypothesis that zonulin opens small intestinal TJs during the early stages of CD and permits entry of putative allergens into the intestinal submucosa where an autoimmune response is elicited.
  • An increased number of autoimmune diseases are now described whose pathogenesis is associated with a primary dysfunction of intestinal intercellular TJs. These same structures however are used to develop innovative strategies for the delivery of macromolecules normally not absorbed through the intestine.

What does this really mean? Originally it was believed that tight junctions did not move were like cement and thought to provide and unbreakable barrier. However, though several studies they realized that tight junctions actually move quickly and have a coordinated response in our bodies. 

Zonulin is a protein that regulate the permeability of the tight junctions in the digestive tract.

Celiac Disease is an autoimmune disease. In order for someone to develop an autoimmune condition there are three factors that must occur 1) genetic predisposition 2) an environmental trigger 3) increased intestinal permeability or leaky gut syndrome; therefore, everyone who has celiac disease already has a leaky gut. So understanding this is crucial to your/our health.

Leaky gut, this is a breaching of the intestinal barrier where toxins and microorganisms break through the tight junctions (cells where their membranes are supposed to be fused together and there is no space; but, in these instances there is space) and now these toxins and microorganisms have unobstructed access to your bloodstream. And this is how you become allergic to many foods that are currently in your now gluten free diet. Your body is on overdrive so to speak and because larger molecules of food are not being stopped by the tight junctions and are going directly into your bloodstream - your body thinks this larger molecule of food is a foreign invader (like gluten) and it attacks everything that gets through these barriers.


Photo credit: google images -


If you have an autoimmune disease your body has been fighting a long time. You have been feeding your body the wrong foods unknowingly and this is why it is crucial to learn what foods you can eat. Learn how to take care of your body and ultimately how to heal your body. It all really begins by understanding what your body is doing and why. Once you understand this, you will be able to make your bodies job easier by feeding it the right and better foods for it to function properly and stop making your body fight every time you put something in your mouth.

So the question becomes now knowing all that your body is going through, isn’t it a whole lot harder to even think about eating those old tempting foods, don’t you think? Would love to hear your thoughts about this, please comment below.

And, should you need some additional help I'm here for you, feel free to check out my other blog posts and my book if you need more information (it’s full of goodies) Gluten Free Guide to a Healthy-Do-Over

* Here’s my little disclaimer, I’m not a doctor, researcher, immunologist, just someone deeply concerned and trying to help as many peeps as I can make conscious, good, healthy choices for their health and their bodies when living life with gluten challenges. I have not been compensated or obligated to write this article, and as always, all thoughts and opinions are honest and my own!