Non-Celiac Immune Responses to Gluten

Rejecting bread due to gluten sensitivity

As a lifestyle change, eliminating gluten seems to have helped many patients recover from longstanding health issues. More and more Americans are choosing not to consume gluten.1 Despite some high-profile commentaries to the contrary,2 many clinicians continue to demonstrate positive results when patients eliminate gluten from their diets. It’s clear why this works for those with frank celiac disease, but the mechanisms are somewhat less clear for patients with gluten sensitivity, as well as for those with no known gluten reactions. A study from the lab of Alessio Fasano, MD, illuminates the impact of gluten on the gut and its role in the development of issues unrelated to celiac.

The study explored the effects of the protein gliadin on the integrity of the intestinal barrier. Gliadin is a component of gluten that triggers immune responses in some patients. Researchers took duodenal biopsies from four populations: patients with active celiac disease, patients with celiac in remission, patients with gluten sensitivity, and patients with no known gluten reactions. In all of the groups, intestinal permeability was significantly increased by exposure to gliadin. Altered gut barrier function was especially pronounced for those with active celiac disease and those with gluten sensitivity.3 A different study found that a subset of patients who were consuming gluten-containing foods had systemic immune activation correlated with intestinal epithelial damage (measured with FABP2) in both the non-celiac wheat-sensitive group and the celiac group, but not in healthy controls.4

Dr. Fasano has posited that many autoimmune diseases develop in the presence of three factors: genetic predisposition, environmental trigger, and intestinal permeability.5 If this research proves to be correct, eating gluten could increase the risk of autoimmune disease for all patients who have a genetic susceptibility, not just those with gluten intolerance.

Food can be medicine, or it can undermine health. At IFM’s Immune Advanced Practice Module (APM), an expert team of clinicians presents several clinical strategies for assessing and treating intestinal permeability as a way to prevent or improve autoimmune conditions, as well as a host of other extra-intestinal issues.

Register for the Immune APM


  1. Choung RS, Unalp-Arida A, Ruhl CE, Brantner TL, Everhart JE, Murray JA. Less hidden celiac disease but increased gluten avoidance without a diagnosis in the United States: findings from the National Health and Nutrition Examination Surveys from 2009 to 2014 [published online December 5, 2016]. Mayo Clin Proc. doi:10.1016/j.mayocp.2016.10.012.
  2. Velasquez-Manoff M. The myth of big, bad gluten. New York Times Sunday Review. July 4, 2015:SR6. Accessed August 22, 2017.
  3. Hollon J, Puppa EL, Greenwald B, Goldberg E, Guerrerio A, Fasano A. Effect of gliadin on permeability of intestinal biopsy explants from celiac disease patients and patients with non-celiac gluten sensitivity. Nutrients. 2015;7(3):1565-1576. doi:10.3390/nu7031565.
  4. Uhde M, Ajamian M, Caio G, et al. Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease. Gut. 2016;65(12):1930-1937. doi:10.1136/gutjnl-2016-311964.
  5. Fasano A. Leaky gut and autoimmune diseases. Clin Rev Allergy Immunol. 2012;42(1):71-78. doi:10.1007/s12016-011-8291-x.

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