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Gluten and Inflammation: The Science Behind it and What You Need to Know

gut inflammation

Virtually everyone has heard about gluten-free diets. A gluten-free diet is medically necessary for those with celiac disease, an autoimmune condition. It can be thought of as an extreme allergy to gluten. Those with celiac disease incur damage to the intestinal tract when they eat wheat gluten, leading to weight loss, iron deficiency, diarrhea, fatigue, and malabsorption. People also avoid gluten because it gives them unpleasant symptoms or they just want to be healthier. In this post I discuss the real science behind the problem with wheat gluten and inflammation.

What is Gluten?

Gluten is a mixture of proteins present mostly in wheat, but also in barley, rye and oat. Gluten is the main protein in wheat, constituting approximately 80% of the total proteins in this grain. Gluten is very resistant to digestion. [1] Therefore, some people get bloated when they eat gluten.[2] There are two subtypes of gluten in wheat called gliadin and glutenin. Gliadin is a protein and Glutenin is a protein responsible for the strength in elasticity of bread dough.

Gliadin also has four subtypes recognized by the immune system:

    • Alpha-gliadin
    • Beta-gliadin
    • Gamma-gliadin
    • Omega-gliadin

It is possible to be allergic to wheat. This is measured through a blood test and there should be no confusion here either. Confusion arises when gluten-free diets are recommended because “it’s just healthier” or “reduces inflammation.”

Athletic coaches, naturopathic doctors, and nutritionists will often recommend a gluten-free diet because it is anti-inflammatory. Many other people go gluten-free to lose weight or to improve intestinal health. In this post I will specifically talk about gluten and inflammation and its role in the immune system.  I will not discuss celiac disease because all patients with this condition must completely avoid gluten from wheat, barley, oats and rye. The complete list of grains containing different types of gluten are:

  • Spelt
  • Kamut
  • Triticale
  • Durum
  • Einkorn
  • Farina
  • Semolina
  • Couscous
  • Barley
  • Rye

Gluten can activate the immune system in a negative way as it is pro-inflammatory. [3] Wheat gluten has been shown to elicit several negative side effects in the body. These include triggering leaky gut (also known as increased intestinal permeability), disturbances of the delicate balance of bacteria in our gut/microbiome, increased oxidative stress, and even changes to the way our genes express themselves.

Non-celiac Gluten Sensitivity

Other than celiac disease there are two other disorders that are triggered by gluten. The first is called non-celiac gluten sensitivity (NCGS). In this condition gluten triggers an autoimmune response. Symptoms may go away when gluten is removed from the diet. Common autoimmune diseases include rheumatoid arthritis, Hashimoto’s thyroiditis (the most common cause of hypothyroidism), ulcerative colitis (UC), inflammatory bowel disease (IBS), multiple sclerosis (MS), and psoriasis. It should be noted that Hashimoto’s thyroiditis may be caused by non-celiac gluten sensitivity. There are even a number of subtypes of non-celiac gluten sensitivity!

These NCGS subtypes include: [4] brain fog, headache, leg or arm numbness, epilepsy and seizure disorders, gluten ataxia (difficulty walking), gluten neuropathy (nerve pain), and gluten encephalopathy (brain disease), depression, anxiety psychosis, schizophrenia, autism, and hallucinations.

The second condition is wheat allergy. Wheat allergy is measured by checking the blood for antibodies. Antibodies are made by the immune system and are a key part of allergies. Checking antibodies is the main way that an allergy is diagnosed.  Between eight and ten percent of the global population are affected by a wheat allergy. [5] An allergy may present in insidious ways. Symptoms may be acute or delayed. Acute symptoms would include gastrointestinal disturbances, fluid retention, increased mucus, and itchy skin. Longer-term symptoms can include lethargy, headache, and gastrointestinal disturbances.

Gluten and dairy free diets are sometimes prescribed for children with learning disabilities or for children with autism spectrum disorder. Peptides found in wheat (gluten exorphin, gliadorphin) and milk (casomorphin) can bind to the opiate receptor in the brain and effect behavior, mood, and immune system.

Gliadin and Immunity

Gliadin is the major protein found in wheat. The genetics of gliadin are different depending on the strain of wheat. Gliadin can activate T cells and trigger a pro-inflammatory immune response. This does not just happen in celiac disease patients. In human studies gliadin increased the release of pro-inflammatory molecules known as cytokines, specifically IL-23, IL-1β and TNF-α.  [6] In the human body, the release of certain cytokines, chemokines, and others either by damaged cells or the immune system, is the main driver of inflammation. In patients with antibodies against gliadin the inflammatory response is enhanced.

For gliadin to interact with the immune system it has to pass through the intestinal barrier to get into the blood and affect the immune system. In people who have increased intestinal permeability (leaky gut) the transport of unwelcome substances through the intestinal barrier is easy. Some human studies show that gliadin can trigger increased intestinal permeability. [7] There are two tests I do to diagnose leaky gut. One is to look for Zonulin found in the stool. The other is a test where the patient drinks a solution and then a urine collection is performed to look for large molecules that should not have passed into the bloodstream. This is called the intestinal permeability test.

Increased Intestinal Permeability and its Association with Disease

Increased intestinal permeability is involved in the genesis of autoimmune diseases such as multiple sclerosis, rheumatoid arthritis, type I diabetes, asthma, chronic fatigue, and even depression. [8] In leaky gut syndrome bits of bacteria and proteins from food enter the circulation and then interact with the immune system. The protein signatures on these sometimes confuse or trick the immune system into attacking its host (also known as molecular mimicry or cross-reactivity). This is what happens in autoimmune disease.

Many aspects of gluten can affect human health in negative ways. These include digestive difficulty, immunological reactions, increased intestinal permeability, actions on the intestinal microbiota, increased oxidative stress and gene expression. It can also affect how long cells live and how they act. Gluten can also kill cells, induce allergy, and elicit a pro-inflammatory response in the body. [9]

The Role of Gluten in Weight Gain

I could not find any good data to support the role of gluten in weight gain which, interestingly, is what started me on the research for this article. There was an animal study that demonstrated fat loss in animals on a gluten-free diet compared to animals eating the same number of calories with gluten. I think human studies need to be conducted because I think most people lose weight when they avoid gluten because there are eating less carbs and/or calories. The same thing happens when people avoid fat, sugar, and animal foods. Placing more restrictions in the diet often leads to less calories which in turn leads to weight loss.

The Scientific Support for Avoiding Gluten

There is good scientific support for avoiding gluten altogether. Throughout the years I have seen improvements in GI function in autoimmune disease symptoms with the removal of gluten in the diet. A trial of gluten avoidance should be initiated for anyone with gastrointestinal difficulties, autoimmune diseases, inflammatory disorders, chronic fatigue, dermatitis, depression or any other condition that does not respond to treatment. Anyone with symptoms that are related to diet should get a complete food allergy test. I like to do one that includes food sensitivities in addition to allergy.

Do not go overboard and cut out all grains. I get concerned when patients go a bit overboard and switch to a completely grain free diet. The fiber in grains is important for health. What I commonly see is an over consumption of high-fat animal products. One should never engage in the consumption foods that cause vascular damage such as bacon, sausage, pork, chicken, cheese, and red meat, to take the place of the calories lost by grains. Perspective is important because whole grains are effective (and preventive) for several conditions. These include strong evidence for the prevention of colon cancer, the lowering of blood pressure, weight loss, and cholesterol-lowering. I do not see any problem avoiding wheat gluten and encourage it as an experiment. There are plenty of other grains to eat instead such as brown rice, quinoa, corn, teff, oats, buckwheat, other ancient grains and a variety of gluten-free breads. Some people can be sensitive to all glutens. This can only be determined through a comprehensive food allergy test.

Also, please do not try to do all the guess work yourself. There are accurate tests that can measure inflammation, allergy, intestinal permeability, intestinal microbiota, autoimmune disease, and virtually every process in the body. Many of these tests are not typically covered by insurance and require special training to understand. Seek a medical professional who is knowledgeable and adept at running sophisticated functional medicine style testing.

Contact us to make an appointment to discuss your GI health concerns: 303-884-7557.


[1] Balakireva AV, Zamyatnin AA. Properties of Gluten Intolerance: Gluten Structure, Evolution, Pathogenicity and Detoxification Capabilities. Nutrients. 2016;8(10):644. Published 2016 Oct 18. doi:10.3390/nu8100644

[2] Aaron Lerner, Yehuda Shoenfeld, Torsten Matthias, Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease, Nutrition Reviews, Volume 75, Issue 12, December 2017, Pages 1046–1058

[3] Lerner A, Benzvi C. “Let Food Be Thy Medicine”: Gluten and Potential Role in Neurodegeneration. Cells. 2021;10(4):756. Published 2021 Mar 30. doi:10.3390/cells10040756

[4] Vazquez-Roque MI, Camilleri M, Smyrk T, Murray JA, Marietta E, O’Neill J, Carlson P, Lamsam J, Janzow D, Eckert D, Burton D, Zinsmeister AR. A controlled trial of gluten-free diet in patients with irritable bowel syndrome-diarrhea: effects on bowel frequency and intestinal function. Gastroenterology. 2013 May;144(5):903-911.e3. doi: 10.1053/j.gastro.2013.01.049. Epub 2013 Jan 25. PMID: 23357715; PMCID: PMC3633663.

[5] Sharma N, Bhatia S, Chunduri V, Kaur S, Sharma S, Kapoor P, Kumari A, Garg M. Pathogenesis of Celiac Disease and Other Gluten Related Disorders in Wheat and Strategies for Mitigating Them. Front Nutr. 2020 Feb 7;7:6. doi: 10.3389/fnut.2020.00006. PMID: 32118025; PMCID: PMC7020197.

[6] Troncone R, Jabri B. Coeliac disease and gluten sensitivity. J Intern Med. 2011 Jun;269(6):582-90. doi: 10.1111/j.1365-2796.2011.02385.x. PMID: 21481018.

[7] de Punder K, Pruimboom L. The dietary intake of wheat and other cereal grains and their role in inflammation. Nutrients. 2013 Mar 12;5(3):771-87. doi: 10.3390/nu5030771. PMID: 23482055; PMCID: PMC3705319.

[8] Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012 Feb;42(1):71-8. doi: 10.1007/s12016-011-8291-x. PMID: 22109896.

[9] Lerner A, Shoenfeld Y, Matthias T. Adverse effects of gluten ingestion and advantages of gluten withdrawal in nonceliac autoimmune disease. Nutr Rev. 2017 Dec 1;75(12):1046-1058. doi: 10.1093/nutrit/nux054. PMID: 29202198.