July 28, 2016
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Researchers find biological explanation for non-celiac wheat sensitivity

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Individuals who experience sensitivity to wheat in the absence of celiac disease or wheat allergy had compromised intestinal epithelial barrier integrity and resulting systemic immune activation, according to the results of a new study published in Gut.

These findings may represent a biological explanation for non-celiac wheat sensitivity, researchers concluded.

“Our study shows that the symptoms reported by individuals with this condition are not imagined, as some people have suggested,” Peter H. Green, MD, the Phyllis and Ivan Seidenberg Professor of Medicine and director of the Celiac Disease Center at Columbia University Medical Center, said in a press release. “It demonstrates that there is a biological basis for these symptoms in a significant number of these patients.”

Peter H. Green

Green and colleagues collaborated with researchers from the University of Bologna, Italy, to investigate whether non-celiac wheat sensitivity involves systemic immune activation in response to translocated microbial products, whether this is linked to intestinal epithelial damage, and whether either of these factors is responsive to elimination of dietary wheat and related cereals.

They evaluated serum samples from 80 individuals who met criteria for non-celiac wheat sensitivity, 40 with celiac disease and 40 healthy controls, both on and off restrictive diets.

Serological markers of innate systemic immune activation (lipopolysaccharide-binding protein [LBP] and soluble CD14 [sCD14]) were not elevated in patients with celiac disease compared with healthy controls, suggesting “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,” according to the press release.

Furthermore, the intestinal cytotoxic T cells seen in patients with celiac disease were not present in the serum samples of patients with non-celiac wheat sensitivity. However, the patients with non-celiac wheat sensitivity had higher concentrations of fatty acid-binding protein 2, a marker of intestinal epithelial cell damage, compared with healthy controls (P < .0001), and this marker correlated with concentrations of LBP, sCD14 and other markers of systemic immune activation. These findings “suggest that the identified systemic immune activation in [non-celiac wheat sensitivity] 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,” according to the press release.

Finally, markers of immune activation and intestinal epithelial cell damage normalized in patients with non-celiac wheat sensitivity after excluding dietary wheat and related cereals for 6 months, and their intestinal and extraintestinal symptoms also improved (P < .0001).

“A systemic immune activation model would be consistent with the generally rapid onset of the reported symptoms in people with non-celiac wheat sensitivity,” Armin Alaedini, PhD, assistant professor of medicine at Columbia University Medical Center, said in the press release. “The data suggest that, in the future, we may be able to use a combination of biomarkers to identify patients with non-celiac wheat sensitivity, and to monitor their response to treatment.”

The researchers plan to further explore the mechanisms that trigger damage to the intestinal epithelial barrier and further characterize the immune cell responses.

“These results shift the paradigm in our recognition and understanding of non-celiac wheat sensitivity, and will likely have important implications for diagnosis and treatment,” Umberto Volta, MD, professor of internal medicine at the University of Bologna, said in the press release. “Considering the large number of people affected by the condition and its significant negative health impact on patients, this is an important area of research that deserves much more attention and funding.” – by Adam Leitenberger

Disclosures: The researchers report no relevant financial disclosures.