Wheat Is A Cause of Many Diseases, I: Leaky Gut

I realized last week that I often call wheat the most toxic food, but I haven’t really explained why on the blog. The book has a detailed explanation, which focuses on toxicity effects and on autoimmune processes attacking the gut and thyroid. Here I would like to add to the book’s argument by showing how wheat causes other autoimmune diseases.

There are about 50 diseases which are thought to have an autoimmune basis. Autoimmune diseases are caused by three processes:

  1. Leaky gut and inflammation. A leaky gut lets bacteria and food toxins enter the body. In the body, these precipitate an immune response which creates inflammation and a chance for antibodies to form.
  2.  “Molecular mimicry.” A bacterial protein or food toxin resembles a human protein sufficiently closely that an antibody to the foreign protein may also recognize human proteins, potentially precipitating attacks on self tissue.
  3. Adjuvant activity. Vaccines are produced by bonding an antigen (the target of the hoped-for antibody) to an adjuvant (a molecule that greatly increases the likelihood antibodies will be made – a sort of catalyst). If a “molecular mimic” can bind to an adjuvant, then autoimmune disease becomes much more likely.

Wheat causes many autoimmune diseases because it promotes all three aspects. I’ll look at each aspect in a separate post this week.

Leaky Gut

In a recent comment – it’s nice to have smart readers! – Rich brought up the links between wheat and leaky gut.

Leaky gut is the first step toward autoimmune disease. As a recent review states:

Susceptibility to at least 50 diseases, including celiac disease (CD) and type 1 diabetes (T1D), has been associated with specific HLA class I or class II alleles. A common denominator of these diseases is the presence of several preexisting conditions that lead to an autoimmune process…. In all cases, increased permeability precedes disease and causes an abnormality in antigen delivery that triggers immune events, eventually leading to a multiorgan process and autoimmunity. [1]

Gluten is a complex of proteins found in wheat, rye, oats (PAJ: see comments), barley, and other grains. One part of gluten is a type of protein called prolamins, which are chiefly responsible for gut damage:

It is the gliadin fraction of wheat gluten and similar alcohol-soluble proteins in other grains (collectively known as prolamins) that are associated with the development of intestinal damage. A common feature of the prolamins of wheat, rye, and barley is a high content of glutamine (>30%) and proline (>15%), whereas the nontoxic prolamins of rice and corn have lower glutamine and proline content. [1]

I’m quoting this because it speaks to the differences among grains. Rice and corn do not contain gluten. Corn contains other dangerous toxins, but is not a primary cause of autoimmune disease. Rice is the only grain we consider safe to eat.

From Cholera to the Cause of Leaky Gut

The mechanisms by which wheat causes leaky gut have been intensively studied by Dr. Alessio Fasano’s group. In 1995 Dr. Fasano and colleagues discovered that a toxin released by Vibrio cholerae, the bacterium that causes cholera http://en.wikipedia.org/wiki/Cholera, causes tight junctions to open for a time. [2] This makes the small intestine leaky.

Dr. Fasano and colleagues suspected that the bacterial protein’s action must mimic some natural human protein which controls intestinal permeability. In 2000, they discovered this human protein and named it “zonulin.” [3]

Wheat and Crohn’s Disease

They subsequently showed that gliadin stimulates zonulin release. Gliadin binds to a receptor called CXCR3, and activation of this receptor triggers zonulin release and increased intestinal permeability.

Interestingly, zonulin release was much higher and longer-lasting in Crohn’s disease patients than in healthy patients. [1] Restriction of gluten restores intestinal integrity in Crohn’s disease patients.

So Crohn’s disease patients should absolutely not eat wheat!

Leaky Gut and Type I Diabetes

A leaky small intestine is a feature of many autoimmune diseases, but Crohn’s disease and Type I diabetes are notable for highly permeable small intestines. Patients with both diseases have high serum levels of zonulin. [1]

In a rat model of Type I diabetes, the BioBreeding diabetes prone or “BBDP” line of rats often develops a leaky gut at age 50 to 75 days when eating a (toxic) diet of rat chow. Zonulin levels increase up to 35-fold at this time, but were reduced if the rats were fed a gluten-free diet. Rats with the highest zonulin levels developed Type I diabetes develops 15 to 25 days later. If a compound that blocks the action of zonulin is given to the rats, Type I diabetes incidence is reduced 70%. [1, 4]

This shows how crucial a leaky gut is to onset of autoimmune diseases like Type I diabetes, and also how quickly diseases can develop once the gut is compromised. The longer the gut is leaky, the greater the likelihood that some autoimmune disease will develop.

In humans, the relationships between these diseases are much the same as in rats. Crohn’s disease and Type I diabetes are co-morbid: the prevalence of Crohn’s among Type I diabetics is 6- to 9-fold higher than in the general population. Meanwhile, newborn children exposed to wheat at 3 months of age or earlier, when the gut is immature, are 4- to 5-fold more likely to develop Type I diabetes. [4]


Leaky gut is a prerequisite for development of autoimmune disease. Wheat seems to create a transient, mild leaky gut in nearly everyone, but in Crohn’s disease the gut becomes chronically and severely leaky in response to wheat consumption.

In rats, this leaky gut can lead to development of autoimmune diseases like Type I diabetes in as little as a few weeks.

If you eat wheat, it’s probably only a matter of time before you develop some disease or other. All of the autoimmune diseases, from rheumatoid arthritis to Hashimoto’s to lupus, are made more likely by wheat consumption. Why not switch to rice or other “safe starches” and save yourself some trouble?

Related Posts

Other posts in this series:

  1. Why Wheat Is A Concealed Cause of Many Diseases, II: Auto-Antibody Generation. Oct 28, 2010.
  2. Why Wheat Is A Concealed Cause of Many Diseases, III: Adjuvant Activity Nov 1, 2010.


[1] Visser J et al. Tight junctions, intestinal permeability, and autoimmunity: celiac disease and type 1 diabetes paradigms. Ann N Y Acad Sci. 2009 May;1165:195-205. http://pmid.us/19538307.

[2] Fasano A et al. Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro. J Clin Invest. 1995 Aug;96(2):710-20. http://pmid.us/7635964.

[3] Wang W et al. Human zonulin, a potential modulator of intestinal tight junctions. J Cell Sci. 2000 Dec;113 Pt 24:4435-40. http://pmid.us/11082037.

[4] Watts T et al. Role of the intestinal tight junction modulator zonulin in the pathogenesis of type I diabetes in BB diabetic-prone rats. Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2916-21. http://pmid.us/15710870.

Leave a comment ?


  1. Hi Paul,

    I recently finished reading PHD and have adjusted my diet in line with PHD from what was a Paleo based diet of the last 12 months.

    I came across a news article today citing the following:

    “A study of 44,500 people in England and Scotland showed vegetarians were 32% less likely to die or need hospital treatment as a result of heart disease.”

    The study was undertaken by the Oxford University with the results published in The American Journal of Clinical Nutrition.

    I am certainly not about to abandon my PHD lifestyle as the health benefits I am experiencing from 12 months of Paleo eating have already convinced me that my previous grain heavy diet was a disaster for my health.

    Just curious to get your take on the study.

    Best regards

  2. Shieldmaid’s Guide to PaleoWorld | Shieldmaid - pingback on May 31, 2013 at 5:15 am
  3. Have you seen Sarah Ballantyne’s blog? She healed her autoimmune disease by eliminating *all* food triggers that causes her immune system to flare up. (See http://www.thepaleomom.com/tag/sarah-ballantyne)

    I think that autoimmune disease is originally caused by leaky gut, which allows large foreign proteins to come into the blood. These proteins cause low-grade inflammation through the innate immune system, but do not initially cause autoimmune issues. However, when an infectious agent is encountered, the infection ramps up the adaptive immune system and, because the leaky-gut foreign proteins are present, can cause the immune system to create antibodies to them as well, and to “learn” that these proteins are dangerous. So in the future, any exposure to these foreign proteins causes B cells to ramp up their antibody production and can cause T cells to ramp up as well.

    So the body is not trying to kill its own cells or create problems with its metabolism — it thinks it is fighting a serious infection, signaled by the foreign proteins leaking through the gut, or recognized by the gut-centric immune system.

    This theory seems to fit all/most autoimmune diseases, and when you eliminate *all* foods that trigger an immune response, the auto-immune disease goes into complete remission. Of particular note is that B-cell-created antibodies have a half-life of about 2 weeks, and eating a trigger for an autoimmune issue will usually cause a “flare” for 1-3 weeks. Sarah says that every time she ate a trigger food, she had two weeks of flared lichen planus, we’ve had similar experiences with our food sensitivities.

    Of course, the infectious agent that upregulates the adaptive immune system could be gut bacteria as part of the leaky gut…

    This also explains why taking digestive enzymes helps many people with auto-immune issues. The enzymes break down the larger proteins that would trigger an immune response.

    If this is all correct, then the cure for auto-immune diseases is to just stop eating foods that trigger an immune response. (And healing a leaky gut would prevent future triggers from being created.)

    BTW, a recent study suggests that insulin resistance is an auto-immune disease: http://med.stanford.edu/ism/2011/april/engleman.html

  4. Hello Paul!

    Thank you for this valuable information. I had a question about alopecia areata (sp?) I have it and now my son who is 4 has it. I have switched to a GAPS diet and he has adapted to it well, I have seen growth but I feel like he is missing carbs. He is still very active and happy and healthy! Guess my question is, will your diet reverse this issue? Thank you for your time!

    A very motivated for change mama!!

  5. Also, how do you heal a leaky gut? Is GAPS the only way?

    • Hi Kristy,

      I think PHD is better than GAPS in most cases for healing a leaky gut, but there are particular mixes of gut bacteria that respond best to starch elimination as in GAPS.

      1. Eat liver (vitamin A) and optimize vitamin D via sun and supplements. This is for mucosal immunity.
      2. Eat collagen rich foods (joints, bones) and extra vitamin C to improve gut barrier.
      3. Eat a balanced nourishing diet without excess nutrition.
      4. Do intermittent fasting.
      5. Eat fermented foods; make fermented vegetables at home.
      6. Tend to circadian rhythms as in chapter 42 of our book.

      You are right that your son is missing carbs. Optimal carbs for a 4 year old is ~35% of energy. Children should eat starches.

      Best, Paul

  6. Thank you so much for getting back to me. The GAPS diet has put so much fear into me about how to eat. All I want are vibrant healthy boys (I also have a 2 year old ) on GAPS. Always hungry. How much vitamin D and C is good for him? Is intermittent fasting also good for my 4 year old? I have your old book, do you talk about circadian rhythms her on your site?

    Thank you SO much again!

    • They shouldn’t be hungry. Eating too few carbs will make them hungry. They need a balanced diet to minimize hunger (and this will work best for the gut too).

      Vitamin D — they should get two hours of sun exposure a day, expose a lot of skin. Vitamin C, it is hard to say because every case is different. Not so much as to produce diarrhea, gas, or queasiness. I suggest getting some powder and giving them vitamin C flavored water to drink. If they get enough C they won’t want it any more.

      Young children should just eat when they are hungry but don’t force them to have breakfast.

      I haven’t said a lot about circadian rhythms on the site.

  7. Sorry, one more thing. By “excess nutrition” are your talking about supplements?


  8. Thank you for this post. I read it about a year ago. I’d like to make one suggestion.

    You state: “Restriction of gluten restores intestinal integrity in Crohn’s disease patients.”

    Perhaps a better statement would be “Restriction of gluten *improves* intestinal integrity in Crohn’s disease patients.”

    I say that because Crohn’s is caused by mycobacterium avium paratuberculosis (MAP), which itself has been shown to cause leaky gut http://iai.asm.org/content/81/11/3960.full?sid=54adc2c6-4ca5-4e85-b0ed-6dc1ad309ea8

    An initial look at the global expression pathways of the host has shown a circumvention of the cell communication pathway by M. avium subsp. paratuberculosis, which loosens the integrity of the tight junctions.

    So removing wheat alone is not sufficient for Crohn’s patients (though it will help). The bacteria must also be killed. For that I recommend John Brisson’s book Fix Your Gut

  9. Nick Retallack

    “developed Type I diabetes develops” – fix this

  10. http://www.wired.com/2015/03/fat-sick-blame-grandparents-bad-habits/
    A new article that states epigenomes can be passed down from generation to generation and we are affected by our parents habits.
    I feel great eating wheat and was wondering whether some people could already be better adapted for processing the wheat toxins?

  11. Dear Christian, why don't you ...? - Page 7 - Christian Forums - pingback on April 13, 2015 at 12:08 pm
    • It looks like when people stopped gluten, they started getting less fiber in their diets. That could be because wheat was a major source of fiber in their diets, or because wheat was suppressing digestion of carbs, leaving more for bacteria. I’d say it’s important to cook and then refrigerate the “safe starches” in your diet to form resistant starch before eating. Also to aim for whole foods, like rice and potatoes, rather than gluten-free flour products like cookies and breads.

      • Hi Paul,

        This idea of cooling safe starches to increase resistant starch seems well established, but I haven’t seen any coverage of how to approach reheating them (if that matters at all). Just wondering if we know anything about the method/extent of reheating reversing the resistant starch formation?


  12. Hi Paul,

    I started experiencing something strange recently that I would love your opinion on. Background: in April I started Bactrim antibiotics for 3 months to help with acne. This is not the first time I have used Bactrim for acne with success, and I did not experience any negative side effects. Around the end of the 3 months I started feeling the sensation of needing to pee all the time (without necessarily actually needing to pee. By the way, I had never had a UTI before.) I went to a urologist and found out that I did have an infection (which I believe technically should have been cured by the Bactrim as it was double strain). I took a 5 day course of nitrofurantoin, and afterwards still had the infection. I then took a 5 day course of keflex. Right before I started taking the keflex I noticed a slightly uncomfortable feeling in my throat, that continued on and off. About 2 days after finishing the course of keflex I noticed my throat feeling significantly swollen after eating (this happened somewhat suddenly, 3 meals in a row). I started eating only fruit, veggies, gluten free bread and protein for the next 3 days, and my throat did not seem to swell as much. I then went back to eating normal food (I do not follow any type of strict diet – so I consume lots of gluten, sugar etc. but don’t eat classic “junk food” and try to eat my veggies..) Anyways, returning to normal food went fine. My throat did not feel irritated the same way. I went to an allergist and was told I have zero food sensitivities. I continued my normal routine with no problems. About a week later my throat started feeling slightly irritated/swollen again and I also started to feel achy with joint pain and a light headache. (It should be noted that I started a long road trip during this time with roughly 6 hours a day in the car). This time I became more concerned and researched incessantly. I started eating only veggies, meat, fish, and eggs. I am thinking this is leaky gut/further complications due to the proximity and suddenness of the issues to the antibiotics. Even now, when I eat an avocado my throat feels strange afterwards. I bought some high quality probiotics which I have been taking. I am wondering if you have an opinion on next steps to take. What kinds of doctors would you recommend seeing, and what tests/blood panels etc. might be good to request? I also read that L-glutamine is a good supplement to take for gut repair – thoughts on that? I was also recommended chlorophyll supplements. This whole situation is very strange and I’m feeling lost (assuming the worst). I am 25 and have always been slender/relatively active. I have never had an issue like this before. Any advice or thoughts you have would be greatly appreciated.

    P.s. I do not have confirmation that the infection was cured by the keflex – I did not do another urine test because I left for the road trip. The peeing issues generally feel better than before but possibly still irregular.

    • Hi Lauren,

      It was a mistake to take so many antibiotics. Acne can readily be cleared by improved nutrition. Killing off your good microbes as you did makes you vulnerable to all sorts of infections, including fungal infections that are not treatable with antibiotics.

      Fortunately it should be easy to recover. Supplement extra vitamin A and D for a while, then optimize them per our book. Also get extra glycine, taurine, N-acetylcystine, and C; and follow our other supplement advice. Intermittent fasting and circadian rhythm entrainment. Try to restore microbial diversity, but don’t do anything dramatic – just eat a diverse natural whole foods diet including raw vegetables and occasional fermented foods.

      Best, Paul

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