Non-celiac gluten sensitivity: questions still to be answered despite increasing awareness

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and extraintestinal symptoms that occur shortly after the ingestion of gluten and improve or disappear when gluten is withdrawn from the diet.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.

High Proportions of People With Nonceliac Wheat Sensitivity Have Autoimmune Disease or Antinuclear Antibodies

“…In addition, in this respect, we and others have suggested that NCWS cannot be considered a unique condition, but rather an "umbrella" term that includes various conditions with different types of pathogenesis. 12,[29][30][31][32][33] Regarding our previous hypothesis that NCWS could be an allergic disease, 28 it should also be remembered that negative IgE test results cannot exclude food allergy. In the absence of specific biomarkers, we should cautiously indicate that this high frequency of autoimmunity can apply to NCWS patients who react to a challenge with a low amount of wheat (equivalent to about 20 g bread in our experiment).…”

Truths, Myths and Needs of Special Diets: Attention-Deficit/Hyperactivity Disorder, Autism, Non-Celiac Gluten Sensitivity, and Vegetarianism

“…RCTs with exclusion and challenge with colorants have demonstrated improvement of hyperactivity in 10-30% of patients [29][30][31] . A meta-analysis of RCTs with colorant elimination diet suggests a modest but consistent effect in non-selected ADHD patients [32][33][34] . This percentage may even increase when the intervention is applied to selected patients with symptoms suggestive of food allergy [2] .…”

Beyond gluten: role of FODMAPs and other wheat proteins as triggers of symptoms in food intolerance

“…NCW/GS is characterized by a wide array of gastrointestinal and extra-intestinal symptoms, occurring shortly after gluten ingestion, improving or completely vanishing in a few hours/days when gluten is withdrawn from the diet and recurring rapidly when gluten is reintroduced (11)(12)(13)18). A mandatory pre-requisite for suspecting this condition is to rule out the diagnosis of both CD and WA when patients are on a gluten-containing diet.…”

“…In the last years the experts of @ C I C E d i z i o n i I n t e r n a z i o n a l i gluten related disorders have started to work intensively on this condition as shown by three Consensus Conferences: one held in London (2011) (12); the other in Munich (2012) (13); and, finally, the third one in Salerno (2015) (27). Furthermore a remarkable number of peer-review papers and reviews on this topic have been published (11,18,(28)(29)(30)(31)(32). Although there is a general agreement that NCW/GS does exist, our knowledge on this syndrome is still lacking with many unsettled aspects.…”

“…Due to a presumed diagnosis of NCW/GS many subjects start GFD without ruling out CD (46). Sometimes, this turns out to be an inappropriate dietary restriction leading to nutritional deficiencies with clinical consequences (18). Therefore a diagnosis of NCW/GS should be always posed in a referral centre following a careful clinical evaluation (23).…”