This little molecule, Zonulin, has quite a story…
Zonulin Is The “Doorway” To Leaky Gut
Zonulin opens up the spaces between the cells of the intestinal lining. That normally occurs, in order for nutrient and other molecules to get in and out of the intestine. However, when leaky gut is present, the spaces between the cells open up too much allowing larger protein molecules to get into the bloodstream where an immunologic reaction can take place. Once that happens, the body is primed to react to those proteins each and every time they appear. It can also cause leakage of intestinal contents, like bacteria into the immune system creating inflammation and overloading the liver's ability to filter out this garbage.
Triggers That Open The Zonulin Doorway
Based on Dr. Fasano's research, we know that the two most powerful triggers to open the zonulin door are gluten and gut bacteria in the small intestine. Gliadin causes zonulin levels to increase both in those people who have celiac disease and those who do not. As the zonulin level rises, the seal between the intestinal cells diminishes, opening up spaces between cells that allow all sorts of things to pass right through. This is called “leaky gut”. Its as if the security guard that keeps the bad guys out is taking a nap! Sometimes large food molecules will pass through to the immune system. The immune system thinks they are foreign invaders and will mount an immune response leading to food sensitivities. In addition this immune activation leads to more damage to the intestinal cells (called enterocytes) and the gut becomes more inflamed and more permeable or “leaky”. As the damage continues, the microvilli that line the intestines and absorb nutrients become damaged, leading to other nutrient deficiencies.
Top Causes of Increased Zonulin and Development of Leaky Gut:
- Overgrowth of harmful organisms, like bacteria or yeast in the intestine
- SIBO = small intestinal bacterial overgrowth
- Fungal dysbiosis or candida overgrowth
- Parasite infections
- Gliadin in the diet (gluten containing foods)
Gliadin is a protein in wheat, that like gluten, is a trigger for people with celiac disease. However, a study published in the Scandiavian Journal of Gastroenterology in 2006 clearly showed that gliadin can affect zonulin even in people without the gene for celiac. The researchers concluded that
Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.
The significance of this is that gluten affects intestinal permeability in all persons to different extents. It also means that 100% of patients with autoimmune disease or leaky gut could potentially benefit from a gluten-free diet.
Elevated Zonulin Levels And Leaky Gut Are Also Associated With The Following:
- Crohn's disease
- Type 1 Diabetes
- Multiple Sclerosis
- Asthma
- Glioma
- Inflammatory Bowel Disease
Genetic predisposition, miscommunication between innate and adaptive immunity, exposure to environmental triggers, and loss of intestinal barrier function secondary to the activation of the zonulin pathway by food-derived environmental triggers or changes in gut microbiota all seem to be key ingredients involved in the pathogenesis of inflammation, autoimmunity, and cancer. This new theory implies that [once this path is activated] it can be… reversed by preventing the continuous interplay between genes and the environment.
Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer
Abstract:
The primary functions of the gastrointestinal tract have traditionally been perceived to be limited to the digestion and absorption of nutrients and to electrolytes and water homeostasis. A more attentive analysis of the anatomic and functional arrangement of the gastrointestinal tract, however, suggests that another extremely important function of this organ is its ability to regulate the trafficking of macromolecules between the environment and the host through a barrier mechanism. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiological modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the finely tuned zonulin pathway is deregulated in genetically susceptible individuals, both intestinal and extraintestinal autoimmune, inflammatory, and neoplastic disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by reestablishing the zonulin-dependent intestinal barrier function. This review is timely given the increased interest in the role of a “leaky gut” in the pathogenesis of several pathological conditions targeting both the intestine and extraintestinal organs.
24 Comments
I was just blown away by this article. Although my emphasis is on environmental health factors such as toxins, mold exposure and indoor air pollution and their toxic influence on health, the discovery of Zonulin and its influence of a diet gluten on the gut linked to such conditions as asthma, Type 1 diabetes, Crohn’s disease,MS… is should be noted and action must be taken accordingly. With so many people suffering from such conditions as irritable bowel disease with no relief, I am confident that this could be Zonulin could be related and perhaps a gluten free diet and maybe some environmental controls could help digestive issues. Note, I am no way a health professional; just someone throwing some thoughts out there for those that do the research and those that practice.
Lots more research done since you wrote this post.
Glyphosate is looking like the worst villain regarding zonulin, tight junctions, and leaky gut.
See the work of Biomic Sciences, with this summary article:
http://tightjunctions.com/cause-gluten-intolerance-plot-thickens/
or this peer-reviewed journal article:
http://clinical-nutrition.imedpub.com/protective-effects-of-lignite-extract-supplement-on-intestinal-barrier-function-in-glyphosatemediated-tight-junction-injury.pdf
Samsel and Seneff’s article is much cited:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3945755/
Thanks for sharing, Burt!
There are scientists that believe cells in our gut and digestive system can get stressed by directly glyphosate (Roundup herbicide) or indirectly by undigested gluten (as a result of glyphosate caused digestive disorder), and these stressed cells then release Zonulin – which in turn triggers the leaky gut syndrome.
Any comment on the glyphosate-zonulin-leaky gut pathway?
Yes, you are correct… glyphosate does induce intestinal permeability
Is it just gluten that needs to be removed for the barriers to start healing again can anything else help improve it along the way?
yes, Tara, you can do elimination diet, glutamine powder and probiotics
Dr. Jill,
What if I have dysbiosis? Besides an elimination diet, glutamine powder and probiotics, do I need to figure out how to get rid of the bad bacteria? My GI doctor has me on Enteragam to help with diarrhea and absorb more nutrients and help stop the weight loss.
Dear Dr. Jill, I’m so happy to find your website. 20 years of increasingly bad food sensitivities. I have seen multiple docs including a couple functional docs. I eat a 100% strict Paleo diet with absolutely NO sugar, gluten or grain of any kind. No alcohol, no night shades and I even have to severely restrict fruit. I have been taking pro-biotics, L-glutamine and several other supplements. I’ve tried making and drinking bone broth. And now medical canabis for inflammation as well. Symptoms are eye inflammation (which I mostly have under control) and supra-glottic stenosis, which is inflammation and scarring of my throat, for which I have now had 3 operations to keep me breathing. Unfortunately, I am now on imuron and prednisone as the natural approach obviously isn’t working. But because I’ve been on and off pred so many times, I find that I can’t get off it or I will have a flare up. And now I have gut issues (bloating and constipation) due to the prednisone. I know this is a tall order, especially on email, but I didn’t want your reply to tell me something I have already tried. If you have ANY suggestions for me, please tell me. If you think you could help me at your clinic, I will drive to CO. Thank you so much
Hi Dr. Jill,
Great article. Do you know if any zonulin studies have been done on gluten from organic wheat or Einkorn wheat ? Since glyphosate greatly affects these tight junctions in the gut, I’m wondering if it’s the biggest culprit. Maybe organic wheat or ancient strains of wheat are not that toxic to the average person. Would like to have your insight. Thanks.
I have been gluten free for 22years I have a lot of issues with my nerves. Have had a nerves stomach all my life. When a lot of. Pressure. At work causes me to get. Bloated. And need to drink a lot of water to. Belch to get relief. I have had severe heart burn. With out meds. Got any suggestion. For me try
can leaky gut cause extreme anxiety and insomnia?
Many gut related imbalances can contribute to anxiety and sleep disturbances. I suggest trying a psychobiotic, like ZenBiome Cope
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