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Dr. Jill Carnahan, MD
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Dr. Jill Carnahan, MDDr. Jill Carnahan, MD

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Zonulin: A Discovery That Changed the Way We View Inflammation, Autoimmune Disease and Cancer

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  3. Zonulin: A Discovery That Changed…
Zonulin
An amazing discovery a few years ago revolutionized our ability to understand the gut and permeability and how this impacts a wide range of health conditions from cancer to autoimmune disease to inflammation and food sensitivities.

This little molecule, Zonulin, has quite a story…

 Zonulin

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:

  1. Overgrowth of harmful organisms, like bacteria or yeast in the intestine
    1. SIBO = small intestinal bacterial overgrowth
    2. Fungal dysbiosis or candida overgrowth
    3. Parasite infections
  2. 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:

  1. Crohn’s disease
  2. Type 1 Diabetes
  3. Multiple Sclerosis
  4. Asthma
  5. Glioma
  6. Inflammatory Bowel Disease
In conclusion the article states:

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

Alessio Fasano

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.

* These statements have not been evaluated by the Food and Drug Administration. The product mentioned in this article are not intended to diagnose, treat, cure, or prevent any disease.   The information in this article is not intended to replace any recommendations or relationship with your physician.  Please review references sited at end of article for scientific support of any claims made.

Categories: Autoimmune Health, Gut Health, NutritionBy Dr. Jill C. Carnahan, MD, ABIHM, IFMCPJuly 14, 201322 Comments
Tags: allergiesasthmacancercandidacrohn’s diseasefasanofood sensitivitygliomaglutengluten-freegluten-free dietinflammationleaky gutmultiple sclerosisSIBOzonulin
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Author: Dr. Jill C. Carnahan, MD, ABIHM, IFMCP

https://www.jillcarnahan.com/

Dr. Jill is Your Functional Medicine Expert! She uses functional medicine to help you find answers to the cause of your illness and addresses the biochemical imbalances that may be making you feel ill. She'll help you search for underlying triggers contributing to your illness through cutting edge lab testing and tailor the intervention to your specific needs as an individual. She may use diet, supplements, lifestyle changes or medication to treat your illness but will seek the most gentle way to help your body restore balance along with the least invasive treatment possible. Dr. Jill is a functional medicine expert consultant and treats environmental and mold-related illness as well

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22 Comments

  1. Judy Kojadinovich says:
    July 20, 2013 at 7:21 am

    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.

    Reply
  2. Burt Furuta says:
    April 30, 2017 at 3:31 pm

    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/

    Reply
    • Jill Carnahan, MD says:
      April 30, 2017 at 4:36 pm

      Thanks for sharing, Burt!

      Reply
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  4. Pingback: 5 Ways Gluten Free Can Improve Your Health- Holistic Wellness
  5. Pingback: Why is Gluten so bad for Auto Immunity? – Middle Eats
  6. Tony Mitra says:
    August 29, 2017 at 1:03 pm

    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?

    Reply
    • Jill Carnahan, MD says:
      August 29, 2017 at 3:08 pm

      Yes, you are correct… glyphosate does induce intestinal permeability

      Reply
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  8. Tara O Neill says:
    March 6, 2018 at 6:27 am

    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?

    Reply
    • Jill Carnahan, MD says:
      March 6, 2018 at 2:10 pm

      yes, Tara, you can do elimination diet, glutamine powder and probiotics

      Reply
      • Diane t says:
        July 20, 2018 at 7:25 pm

        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.

        Reply
  9. Pingback: Things that may help those who have the more difficult digestive problems. – Lee's Stuff
  10. Pingback: Inflammation is the cause of chronic illness and infection. To heal you must address inflammation. – Lee's Stuff
  11. Kathy Fears says:
    January 3, 2019 at 5:41 pm

    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

    Reply
  12. Dave says:
    January 30, 2019 at 7:39 am

    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.

    Reply
  13. Pingback: Going From Gluten Free To Grain Free Changed My Life!
  14. Pingback: Could an Unhealthy Gut be the Root of all Disease? | Dr. Seth Gerlach
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  16. Richard pertuset says:
    October 15, 2019 at 5:21 pm

    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

    Reply
  17. Pingback: Is eating wheat bad for you? – Whole Truth Health
  18. Pingback: Why chronic illness had become epidemic and things that may help. – Lee's Stuff

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Dr. Jill
Dr. Jill will help you search for underlying triggers contributing to your illness through cutting edge lab testing and tailor the intervention to your specific needs as an individual.
  • Address:
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