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Review
, 10 (5), 383-92

Non-celiac Gluten Sensitivity: Questions Still to Be Answered Despite Increasing Awareness

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Review

Non-celiac Gluten Sensitivity: Questions Still to Be Answered Despite Increasing Awareness

Umberto Volta et al. Cell Mol Immunol.

Abstract

Recently, the increasing number of patients worldwide who are sensitive to dietary gluten without evidence of celiac disease or wheat allergy has contributed to the identification of a new gluten-related syndrome defined as non-celiac gluten sensitivity. Our knowledge regarding this syndrome is still lacking, and many aspects of this syndrome remain unknown. Its pathogenesis is heterogeneous, with a recognized pivotal role for innate immunity; many other factors also contribute, including low-grade intestinal inflammation, increased intestinal barrier function and changes in the intestinal microbiota. Gluten and other wheat proteins, such as amylase trypsin inhibitors, are the primary triggers of this syndrome, but it has also been hypothesized that a diet rich in fermentable monosaccharides and polyols may elicit its functional gastrointestinal symptoms. The epidemiology of this condition is far from established; its prevalence in the general population is highly variable, ranging from 0.63% to 6%. From a clinical point of view, non-celiac gluten sensitivity is characterized by a wide array of gastrointestinal and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet. These symptoms recur when gluten is reintroduced. Because diagnostic biomarkers have not yet been identified, a double-blind placebo-controlled gluten challenge is currently the diagnostic method with the highest accuracy. Future research is needed to generate more knowledge regarding non-celiac gluten sensitivity, a condition that has global acceptance but has only a few certainties and many unresolved issues.

Figures

Figure 1
Figure 1
Pathogenic mechanisms of NCGS. Enhanced neutrophil recruitment, gut inflammation, changes in intestinal microbiota and immune response to gliadin are features (orange field) common to NCGS and celiac disease. Decreased intestinal barrier function (increased permeability), intestinal mucosa damage and autoimmunity expressed by immune reaction to tissue transglutaminase are typical of celiac disease (red field), whereas enhanced intestinal barrier function (reduced permeability) has been demonstrated in NCGS. AGA, anti-gliadin antibodies; NCGS, non-celiac gluten sensitivity; tTGA, tissue transglutaminase antibodies.
Figure 2
Figure 2
Known triggers of NCGS. Gluten is the primary trigger but not the only trigger of this syndrome because other wheat proteins, such as the wheat ATIs, have been demonstrated to elicit the innate immune response leading to NCGS. Moreover, many NCGS pts display a food hypersensitivity elicited by FODMAPs. Functional gastrointestinal symptoms observed in patients with NCGS as well as with other disorders, including IBS, could also be partly related to food additives, such as glutamates, benzoates, sulfites and nitrates, which are added to many commercial products for a variety of reasons (e.g., to enahnce flavor, color and preservative function). FODMAP, fermentable oligo-, di- and mono-saccharide and polyol; IBS, irritable bowel syndrome; NCGS, non-celiac gluten sensitivity; ATIs, amylase trypsin inhibitors.

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