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Non-celiac gluten sensitivity (NCGS) or gluten sensitivity[14] is defined as "a clinical entity induced by the ingestion of gluten leading to intestinal and/or extraintestinal symptoms that improve once the gluten-containing foodstuff is removed from the diet, and celiac disease and wheat allergy have been excluded".[15]

NCGS is included in the spectrum of gluten-related disorders.[3][4] The definition and diagnostic criteria of non-celiac gluten sensitivity were debated and established by three consensus conferences.[4][14][15][16][17]

The pathogenesis of NCGS is not yet well understood, but the activation of the innate immune system, the direct cytotoxic effects of gluten and probably other wheat components, are implicated.[3][18][19] There is evidence that not only gliadin (the main cytotoxic antigen of gluten), but also other proteins named ATIs which are present in gluten-containing cereals (wheatryebarley, and their derivatives) may have a role in the development of symptoms. ATIs are potent activators of the innate immune system.[3][20] FODMAPs, especially fructans, are present in small amounts in gluten-containing grains and have been identified as a possible cause of some gastrointestinal symptoms in NCGS patients.[3][10][21][20] As of 2019, reviews have concluded that although FODMAPs may play a role in NCGS, they only explain certain gastrointestinal symptoms, such as bloating, but not the extra-digestive symptoms that people with NCGS may develop, such as neurological disordersfibromyalgia, psychological disturbances, and dermatitis.[20][9][3]

For these reasons, NCGS is a controversial clinical condition[22] and some authors still question it.[23][24] It has been suggested that "non-celiac wheat sensitivity" is a more appropriate term, without forgetting that other gluten-containing cereals are implicated in the development of symptoms.[11][23]

NCGS is the most common syndrome of gluten-related disorders[4][25] with prevalence rates between 0.5–13% in the general population.[13] As no biomarker for diagnosing this condition is available, its diagnosis is made by exclusion of other gluten-related disorders, namely by excluding celiac disease and wheat allergy.[22] Many people have not been diagnosed following strict criteria and there is a "fad component" to the recent rise in popularity of the gluten-free diet, which leads to debate surrounding the evidence for this condition, its relationship to celiac disease and to irritable bowel syndrome.[3][5] People with non-celiac gluten sensitivity may remain in a "no man's land", without being recognized by the specialists and lacking the adequate medical care and treatment.[26] Most of these people have a long history of health complaints and unsuccessful consultations with numerous physicians, and this is the reason why many of them end up resorting to a gluten-free diet and a self-diagnosis of gluten sensitivity.[27]

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