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Many people report reacting to wheat, but test negative for coeliac disease and wheat allergy. A new study suggests a possible explanation.

A new study may explain why people who do not have coeliac disease or wheat allergy nevertheless experience a variety of gastrointestinal and extra-intestinal symptoms after ingesting wheat and related cereals. The findings suggest that these individuals have a weakened intestinal barrier, which leads to a body-wide inflammatory immune response. Findings from the study, which was led by researchers from Columbia University Medical Center (CUMC), were reported in the journal Gut.

“Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested,” said study co-author Peter H. Green. “It demonstrates that there is a biological basis for these symptoms in a significant number of these patients.” Researchers have struggled to determine why some people, who lack the characteristic blood, tissue, or genetic markers of coeliac disease, experience coeliac-like GI symptoms, as well as certain extra-intestinal symptoms, such as fatigue, cognitive difficulties, or mood disturbance, after ingesting foods that contain wheat, rye, or barley. One explanation for this condition, known as non-coeliac gluten or wheat sensitivity (NCWS), is that exposure to the offending grains somehow triggers acute systemic immune activation, rather than a strictly localised intestinal immune response.

In the new study, the CUMC team examined 80 individuals with NCWS, 40 individuals with coeliac disease, and 40 healthy controls. Despite the extensive intestinal damage associated with coeliac disease, blood markers of innate systemic immune activation were not elevated in the coeliac disease group. This suggests that the intestinal immune response in coeliac patients is able to neutralise microbial components that may pass through the damaged intestinal barrier, thereby preventing a systemic inflammatory response against highly immunostimulatory molecules.

The NCWS group was markedly different. They did not have the intestinal cytotoxic T cells seen in coeliac patients, but they did have a marker of intestinal cellular damage that correlated with serologic markers of acute systemic immune activation. The results suggest that the identified systemic immune activation in NCWS is linked to increased translocation of microbial and dietary components from the gut into circulation, in part due to intestinal cell damage and weakening of the intestinal barrier. NCWS patients who followed a diet that excluded wheat and related cereals for six months were able to normalize their levels of immune activation and intestinal cell damage markers, the researchers also found. These changes were associated with significant improvement in both intestinal and non-intestinal symptoms, as reported by the patients in detailed questionnaires.