Non-celiac Gluten Sensitivity. Is it in the Gluten or the Grain?

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Petula Nijeboer1, Hetty J. Bontkes2, Chris J.J. Mulder1, Gerd Bouma1

1) Department of Gastroenterology and Hepatology, VU University Medical Center;
2) Department of Pathology, Unit Medical Immunology, VU University Medical Center,
Amsterdam, The Netherlands


Celiac disease is an immune-mediated inflammatory disorder of the small intestine caused by sensitivity to dietary gluten and related proteins in genetically predisposed individuals. Over the past several years, the concept of non-celiac gluten sensitivity (NCGS) has gained significant interest from the scientific community and mass media and the number of individuals embracing a gluten-free diet is rapidly growing. This condition is characterized by gastrointestinal or extraintestinal symptoms that respond to gluten withdrawal without evidence for underlying celiac disease or wheat allergy. Symptoms display significant overlap with the irritable bowel syndrome. Many important factors regarding this relatively novel condition remain to be elucidated; no discriminative markers to support a diagnosis of gluten sensitivity have been identified yet and its pathogenesis remains obscure. Here we review the current knowledge on NCGS, and outline potential pathogenic pathways of different gluten related disorders in order to gain clues about the pathophysiology of this novel condition.

Key words:
gluten sensitivity - non-celiac gluten sensitivity - NCGS - celiac disease - wheat allergy - irritable bowel syndrome - IBS - gluten free diet - grain - wheat

anti-DGP: anti-deamidated gliadin antibodies; anti-EMA: anti-endomysial antibodies; anti- TTG: anti-transglutaminase antibodies; ATIs: α-amylase/trypsin inhibitors; CD: celiac disease; FODMAPs: fermentable, oligo-, di-, monosaccharides, and polyols; GCD: gluten-containing diet; GFD: gluten-free diet; GM-CSF: granulocyte-macrophage colony-stimulating factor; IBS: irritable bowel syndrome; IELs: intraepithelial lymphocytes; IFN-γ : interferon gamma; NCGS: non-celiac gluten sensitivity; PBMC: peripheral blood mononuclear cell; TCR- γδ: gamma delta T-cell antigen receptor; TLR2: toll-like receptor 2; TLR4- MD2-CD14: lipopolysaccharide receptor complex; TNF-α: tumor necrosis factor-alpha; VAS: Visual Analogue Score; WGA: Wheat Germ Agglutinin