By Joseph E. Scherger, MD, MPH

Vice President, Primary Care, Eisenhower Medical Center; Clinical Professor, Keck School of Medicine, University of Southern California

Dr. Scherger reports no financial relationships relevant to this field of study.

SYNOPSIS: Some patients without celiac disease may exhibit wheat sensitivity with demonstrated intestinal epithelial cell damage.

SOURCE: 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. doi:10.1136/gutnl-2016-311964. Published online July 25, 2016.

A team at Columbia University studied 80 individuals who reported on a standardized questionnaire sensitivity to wheat, rye, or barley. Researchers compared these subjects with 40 individuals suffering from celiac disease and 40 healthy individuals exhibiting no symptoms. Those with non-celiac wheat sensitivity (NCWS) experienced intestinal symptoms (bloating, abdominal pain, diarrhea, epigastric pain, and nausea) and extraintestinal symptoms (fatigue, headache, anxiety, memory and cognitive disturbances, and numbness of the arms or legs). These symptoms improved or disappeared when subjects removed wheat, rye, and barley from their diets for six months. The symptoms recurred when subjects reintroduced these food items for up to one month.

The authors performed serum samples and intestinal biopsies on all the study subjects and controls. Those with NCWS did not exhibit the IgA antibodies or TG2 autoantibodies specific for celiac disease. These subjects also did not have the intestinal histologic findings specific for celiac disease. Those presenting with NCWS showed changes in the serum and intestinal epithelium that researchers did not observe in the healthy controls. These findings include increased levels of soluble CD14 and lipopolysaccharide-binding protein, indicating systemic immune activation. NCWS subjects also showed increased levels of fatty acid-binding protein 2, suggesting compromised intestinal barrier integrity. The intestinal biopsies of subjects with NCWS showed epithelial cell damage not seen in healthy controls and that was different from the changes seen in celiac disease. These abnormalities largely resolved during the six months away from the offending foods.


This study provides further biologic evidence for the “leaky gut” changes postulated in patients consuming gluten-containing foods of wheat, rye, and barley. Uhde et al chose to use wheat and related grains as the culprits, since other proteins may be involved beyond the gluten complex of gliadins and glutamines. The prevalence of NCWS is unknown, and it is not clear if most patients complaining of “gluten sensitivity” experience any of these changes.

The range of intestinal and extraintestinal symptoms these patients experience — as well as their resolution after removal of the offending foods — is impressive. These results match with my practice experience. I routinely recommend the removal of wheat, rye, and barley from all patients presenting with gastroesophageal reflux (GERD) and irritable bowel syndrome, with clinical improvement or resolution of symptoms in most patients. I am gratified to wean many patients off proton pump inhibitors or H2 blocking medications. I also find that many patients with chronic fatigue and fibromyalgia symptoms improve or recover with elimination of these foods. The full list of symptoms and diagnoses associated with inflammatory grains is quite long.

This study did not address the association of inflammatory grains with a variety of autoimmune diseases. This area and the role of the gut microbiome have been explored in other reports.1-6

The specific biologic results shown in this controlled study should help us recognize the importance of understanding how inflammatory grains may be harming our patients. The time is now to use an elimination diet with many of our patients.


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  3. Volta U, De Giorgio. New understanding of gluten sensitivity. Nat Rev Gastroenterol Hepatol 2012;9:295-299.
  4. Perlmuter D, Loberg K. Grain Brain. New York: Little, Brown and Co.; 2013.
  5. Mullen G. The Gut Balance Revolution. New York: Rodale; 2015.
  6. Wahls T. The Wahls Protocol. New York: Avery (Penguin Group); 2014.