A new study may explain why people who do not have celiac 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.

Celiac disease is an autoimmune disorder in which the immune system mistakenly attacks the lining of the small intestine after someone who is genetically susceptible to the disorder ingests gluten from wheat, rye, or barley. This leads to a range of gastrointestinal symptoms, including abdominal pain, diarrhea, and bloating.

Researchers have struggled to determine why some people, who lack the characteristic blood, tissue, or genetic markers of celiac disease, experience celiac-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-celiac gluten or wheat sensitivity (NCWS), is that exposure to the offending grains somehow triggers acute systemic immune activation, rather than a strictly localized intestinal immune response. Because there are no biomarkers for NCWS, accurate figures for its prevalence are not available, but it is estimated to affect about 1 percent of the population, or 3 million Americans, roughly the same prevalence as celiac disease.

In the new study, the CUMC team examined 80 individuals with NCWS, 40 individuals with celiac disease, and 40 healthy controls. Despite the extensive intestinal damage associated with celiac disease, blood markers of innate systemic immune activation were not elevated in the celiac disease group. This suggests that the intestinal immune response in celiac patients is able to neutralize microbes or 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 celiac 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.