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Intestinal Permeability: the AutoImmune Connection

Hashimoto’s, Multiple Sclerosis, Lupus, Rheumatoid Arthritis, …. These types of dis-ease in the body seem so different because they attack different parts of the body. However, they are all actually caused by dysfunction of the immune system – an overwrought, confused immune system. The brain, the thyroid, the skin, the joints, etc. are just the various localized battlefields.

With the rapid increase in exposure to processed foods, chemicals, toxins, chronic stress, GMOs, and many other foreign molecules – usually on a daily basis – it shouldn’t be a surprise that our immune system is confused!  To put AI disease in remission, we have to find out why each person’s unique immune system is overwrought and fix it.  I have helped several clients to do this over the years – and many others to experience significant relief, often being able to stop immuno-suppressive drugs.  And you can be a bridge to this type of healing too!  Yes, AI disease can indeed be put into long-term remission.

The true root causes of immune activation are unique for each person.  Usually, it’s a small handful of triggers.  Things like intestinal Yeast overgrowth, lead or arsenic toxicity, undiagnosed food sensitivities, Vitamin D deficiency, B vitamin insufficiency (which leads to poor detox capability), adrenal exhaustion, and/or non-pathogenic bacterial overgrowth such as Clostridia.  There is testing available for all of these things!  It just takes some time to sort out the puzzle pieces.  However, there is one simple change that can begin this journey for all clients with an AI disorder. One thing all auto-immune diseases have in common. Something our clients typically won’t hear from their physicians.  Intestinal permeability.


Yes, genetics can play a role in predisposition for certain AI disorders, but alone, genes are almost never enough to cause activation.  Environment determines which of our genes “turn on”. And a primary way that our body senses and responds to our environment is in the gut.  Intestinal permeability – a.k.a. “leaky gut” – offers a short-cut for chronic inflammatory molecules in the gut (and a myriad microbial and ingested toxins) to rapidly get into our blood supply for systemic circulation.   It is well-understood that some individuals are more vulnerable to leaky gut.  Now at last, it’s also well-understood that gluten – the protein found in many common grains especially wheat – can trigger release of a protein in the human gut called zonulin which actually causes leaky gut.  

 Full gluten elimination from the diet and healing the leaky gut can be very powerful ways to break the cycle of intestinal permeability in our clients with AI disorders.  It’s critical for these clients to understand that the elimination must be complete (cold-turkey!) in order to yield results.  That’s where our role as practitioners can really shine!  Help your clients to find convenient, whole-food, nutrient-dense alternatives.  Teach them how to read labels.  Prepare them for navigating family gatherings.  Practice what to say at a restaurant.  Give them a list of common hidden sources of gluten.  Cheer them on!  And once they have fully eliminated gluten for a couple of weeks, you can help them to begin to heal their leaky gut with supplements that include both l-glutamine (an amino acid that heals damage to the villi in the intestines) and mucilaginous herbs that repair the mucosal intestinal lining (e.g. aloe, DGL).  I really like easy-to-use blends of these two e.g. Metagenics Glutagenics or Designs for Health GI Revive.  There will almost always be other sources of inflammation in the gut that need to be identified and resolved for full intestinal healing (and clients with IBS should work on healing the gut lining until the microbial imbalance is fully addressed).  But this is a powerful way to get started and get them some relief while the rest of the puzzle pieces are put together!  Generally, l-glutamine supplements are very well-tolerated, but there are just a few considerations to ensure you know for potential contraindication.

Here is an excellent article by Dr. Joe Pizzorno summarizing the effect of Zonulin, wheat, and other foods in the etiology of autoimmune disease.  This is great reading if you want to explore this topic more in-depth or share information fodder with a savvy client.

One last tip about supporting autoimmune disorders…  Long-term relief and remission require addressing root causes.  However, Yes indeed, short-term support can help to reduce AI symptoms, especially remedies that calm inflammation at its source and calm immune system activation at its source (in the gut!).  Specifically, I recommend the following for nearly all my adult clients with AI disorders.  These can provide relief while we work together to get to the root cause of their challenges:

  • Herbal anti-inflammatory herb, especially curcumin.  I most often recommend the Meriva form which helps to increase absorption from the gut, 1000mg taken twice daily.
  • Ensure Vitamin D is not insufficient – at least near 50ng/ml.
  • A flavonol found in some fruits and veggies, Quercetin, is an anti-inflammatory extract that has also been clinically shown to repair intestinal permeability.  I typically recommend 500mg twice daily, though some clients may need more, especially if they also suffer some allergies/asthma or chronic nasal/sinus congestion or post-nasal drip (remember to have them try dairy elimination!).
  • ~4 grams l-glutamine powder thrice daily on an empty stomach to help to repair damage to the intestinal lining (be cautious and ramp slowly if there are strong anxiety concerns).  (Those with celiac disease may need substantially more l-glutamine ~10g thrice daily, but again, it’s important to ramp slowly to gauge unique effects.)
  • A daily probiotic that includes Saccharoymyces Boulardii and Lactobacilus Rhamnosus taken twice daily (e.g. Metagenics Acute Care), the former assuming there is no known allergy to yeast.  Both of these particular species have been shown clinical to be strong inflammation mediators (by reducing inflammatory cytokine production – a common biochemical phenomenon in AI disorder).
  • Full elimination of all gluten (to remove likely trigger for ongoing intestinal permeability).  But ideally also all dairy foods and ideally all grains from the diet.  It is common for those with AI disorder to have sensitivities to other grains e.g. oats, corn due to molecular mimicry in the gut that cause the immune system to attack grains beyond wheat.   Elimination of grains can also help to prevent feeding of microbial overgrowth which might be present in the gut.  I don’t recommend suggesting all these to a client at once; it’s too overwhelming!  But once they have mastered gluten, you can move to the next step.

I recently recorded a deeper dive video on intestinal permeability which you might want to check out.  This gut vulnerability is ubiquitous in autoimmune dis-ease, but it is associated with many of dis-ease states..

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16 Questions for “Intestinal Permeability: the AutoImmune Connection”

  1. 8
    Sarah Campbell says:

    You mention an overgrowth (or increased presence of) Clostridia (even though toxin A and B are negative) being a cause of intestinal permeability. Can you give me more detail on addressing this type of overgrowth in a client that suffers from eczema and autoimmune activation? Thank you.

  2. 7
    Jacki Veler says:

    Thank you for the great information!

    My question is to the extent of removing inflammatory foods, like gluten, dairy, etc. Should we advise, or hope to see, our clients treat these elimination diets like they would if it were an allergen? Vigilance about cross contamination, or is simple avoidance of clear sources enough? There are many gluten free options among processed food, (even simply processed food) but that may have been cross contaminated in the processing. Or in restaurants, preparing food is also a cross contamination risk.

    Thank you,

    • 7.1
      SAFM Team says:

      Your question brings up the concept of the individuality as the approach here will heavily depend on the situation of a client – are they barely getting out of bed due to a full-on autoimmune condition or are they generally well and only complaining from occasional joint pain. In the first case, 100% elimination of potentially exacerbating foods is the most healing choice. In the second scenario, they may get away with a marked reduction vs 100% elimination and get their results a bit more slowly but have more ease and food options available. That’s from the perspective of the dis-ease advancement and the health results that a person would like achieve.
      In real life when choices are indeed sometimes limited it may be worth supporting the brush border digestive enzymes with a formula that assists with the breakdown of most common allergens – a few good examples here include ProtectZyme by DFH, Digest Spectrum by Enzymedica or GlutenManager by Integrative Therapeutics and many others. Those enzymes are a nice tool to use to give clients peace of mind while eating out so that they don’t have to worry about the cross contaminations that you are talking about. Those enzyme formulas are not designed to fully replace the food elimination, though.

  3. 6
    sharon chud says:

    On top of the question above if a client has yeast overgrowth would you avoid Sac Boulardi? as a probiotic

    • 6.1
      SAFM Team says:

      S. Boulardi might be beneficial, actually, if there is an intestinal yeast overgrowth because it provides competition, stimulates immune response, and can change up the pH of the environment to be less hospitable to candida. I would not use S. Boulardi, however, if there is a known allergy or sensitivity to yeast or if a person is severely immunocompromised. You might appreciate this: .

  4. 5
    Lisa Verdejo says:

    To confirm my understanding here, I see that gluten is to be eliminated for AI dynamics to mitigate intestinal permeability a la the zonulin release. However, you mention the elimination of all grains due to potential molecular mimicry to gluten. So, therefore, the gluten elimination is also to address a potential IgG (and other potential immune system) response?.

    • 5.1
      SAFM Team says:

      Yes. But also… Molecular mimicry may not be via IgG reaction at all; it may be via IgA reaction (in the mucosal lining) or other immune reactivity modes. Specifically for AI, we are concerned about multiple pathways of exacerbation. A person also may or may not have an IgG sensitivity to gluten, but it needs to be eliminated regardless to the zonulin provocation and its role in IP.

  5. 4
    Ana Paula Robledo Soto says:

    Hi, what is the proper way to use zinc carnosine and DLG licorice in regards to doses and times per day to heal the gut lining?

    • 4.1
      SAFM Team says:

      Alas, this depends on the individual and the extent of the damage. If we are speaking of general IP associated with a chronic autoimmune activation, then I would recommend twice daily dosing on an empty stomach – at least an hour before food (perhaps at bedtime ~3 hrs after finishing dinner and then again late morning?). The bedtime dose is ideal because there will be no interference from any other oral intake (other than perhaps water) for several hours. Perhaps 300-500mg DGL and 100mg zinc carnosine (together) for each dose. You may wish to use zinc carnosine in particular if there is a need to support the *gastric* lining (e.g. gastritis). Otherwise, you might consider a multi-nutrient formula for ease that involves other mucilaginous herbs (with or without l-glutamine) e.g. Thorne’s GI Encap, Pure Encapsulations DGL Plus, or Designs for Health’s GI Revive.

  6. 3
    Heather Conley says:

    So zonulin is also released in those without auto-immune dynamics correct? What causes this from creating intestinal permeability in those folks?

  7. 2
    Lisa says:

    I’m reading blogs in which people recommend taking much higher doses of l-glutamine (e.g. 40g or 80g/day). Any thoughts about such megadoses?

    • 2.1
      SAFM says:

      I personally have never recommended doses this high, and I am unaware of clinical research indicating they are necessary for healing IP. In fact, it’s important that the diet contain a balance of other key amino acids which also help to nourish enterocytes (e.g. arginine); l-glutamine is the primary fuel but not the only one for these cells. I also do not think that megadoses of intake have been studied for safety for ongoing use. This might be of interest to you: . I would also be cautious in known IP to consider the potential neurological effects of high doses of l-glutamine, being cautious to increase dosage slowly, even at the lower levels I mention ( I did specify above a likely higher need specifically for those with celiac disease (which can be gauged given ongoing assessment for other food sensitivities), as the precious intestinal lining in that case is the site of both intestinal permeability and the autoimmune attack itself. I believe people will likely have the best results combining l-glutamine with other supportive agents to nourish and build-up the protective mucosal layer in the intestines as well e.g. .

  8. 1
    Kathleen Mitchell says:

    Hmmm… So if there is a gluten cross reactivity to yeast, then one would want to avoid Sac Boulardi (as a probiotic)?

    • 1.1
      SAFM says:

      Yes – good for you! An excellent connection to make, Kathleen. In my clients with active autoimmune dis-ease, I always recommend a food sensitivity test panel to try to identify foods their immune system is reacting to – either from cross-reactivity with gluten or a separate reaction simply mediated by the intestinal permeability. I wouldn’t say yeast is a particularly common cross-reactive food, but people can definitely have food sensitivities to it. We much more typically see other grains (e.g. corn, oats, quinoa) and dairy foods as cross-reactive.

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