Non-Celiac Gluten Sensitivity (NCGS) is a syndrome characterized by intestinal and extra-intestinal symptoms related to the ingestion of gluten-containing food, in subjects that are not affected by either celiac disease or wheat allergy. Given the lack of a NCGS biomarker, there is the need for standardizing the procedure leading to the diagnosis confirmation. In this paper we report experts’ recommendations on how the diagnostic protocol should be performed for the confirmation of NCGS. A full diagnostic procedure should assess the clinical response to the gluten-free diet (GFD) and measure the effect of a gluten challenge after a period of treatment with the GFD. The clinical evaluation is performed using a self-administered instrument incorporating a modified version of the Gastrointestinal Symptom Rating Scale. The patient identifies one to three main symptoms that are quantitatively assessed using a Numerical Rating Scale with a score ranging from 1 to 10. The double-blind placebo-controlled gluten challenge (8 g/day) includes a one-week challenge followed by a one-week washout of strict GFD and by the crossover to the second one-week challenge. The vehicle should contain cooked, homogeneously distributed gluten. At least a variation of 30% of one to three main symptoms between the gluten and the placebo challenge should be detected to discriminate a positive from a negative result. The guidelines provided in this paper will help the clinician to reach a firm and positive diagnosis of NCGS and facilitate the comparisons of different studies, if adopted internationally.

In a randomized, double-blind, placebo-controlled crossover study of individuals with self-reported non-celiac gluten sensitivity, we found fructans to induce symptoms, measured by the GSRS-IBS. Clinicaltrials.gov no: NCT02464150.

NCT02464150.

Background: Diagnosing coeliac disease (CD) in patients on a gluten-free diet (GFD) is difficult. Ingesting gluten elevates circulating interleukin (IL)-2, IL-8 and IL-10 in CD patients on a GFD. Objective: We tested whether cytokine release after gluten ingestion differentiates patients with CD from those with selfreported gluten sensitivity (SR-GS). Methods: Australian patients with CD (n ¼ 26) and SR-GS (n ¼ 18) on a GFD consumed bread (estimated gluten 6 g). Serum at baseline and at 3 and 4 h was tested for IL-2, IL-8 and IL-10. Separately, Norwegian SR-GS patients (n ¼ 49) had plasma cytokine assessment at baseline and at 2, 4 and 6 h after food bars containing gluten (5.7 g), fructan or placebo in a previous double-blind crossover study. Results: Gluten significantly elevated serum IL-2, IL-8 and IL-10 at 3 and 4 h in patients with CD but not SR-GS. The highest median fold-change from baseline at 4 h was for IL-2 (8.06, IQR: 1.52-24.0; P < 0.0001, Wilcoxon test). The two SR-GS cohorts included only one (1.5%) confirmed IL-2 responder, and cytokine responses to fructan and placebo were no different to gluten. Overall, cytokine release after gluten was present in 22 (85%) CD participants, but 2 of the 4 non-responders remained clinically well after 1 y on an unrestricted diet. Hence, cytokine release occurred in 22 (92%) of 24 'verified' CD participants.Conclusions: Gluten challenge with high-sensitivity cytokine assessment differentiates CD from SR-GS in patients on a GFD and identifies patients likely to tolerate gluten reintroduction. Systemic cytokine release indicating early immune activation by gluten in CD individuals cannot be detected in SR-GS individuals.

Disclosures: Professor Gibson's Department financially benefits from the sales of a digital application and booklets on the low FODMAP diet. He has published an educational/recipe book on diet. AbstractIrritable bowel syndrome-like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non-coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non-coeliac gluten sensitivity is excluded by blinded placebo-controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self-reported non-coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem. The controversy that is non-coeliac gluten sensitivityThere is no more controversial dietary topic in gastroenterology or in the Western community in general than that of the role of gluten in conditions other than coeliac disease or some wheat allergies. It has received considerable lay press attention and has been the subject of several books, multiple reviews and opinion articles in the medical literature, and now an increasing number of interventional studies addressing the issue. There have been expert consensus meetings that have described and legitimized the condition non-coeliac gluten sensitivity (NCGS) and criteria for its diagnosis reported.1 Several blinded, crossover studies have claimed in their conclusions that the presence of NCGS is unequivocally present in a proportion of patients believing they are gluten sensitive, and strong recommendations that gluten-free diet (GFD) should be used in patients with irritable bowel syndrome (IBS) have been made on the basis of such data. Yet the topic remains highly controversial. The aims of this review are to define the basis for such controversy and to hopefully assist in evaluating published data. The root of the controversyApart from emotive issues that pervade popular press and the Internet, there are several aspects in the scientific literature regarding the design of studies and interpretation of results that underlie the ongoing controversy. Attribution of effect.There is little doubt that wheat, rye, and barley can induce symptoms in people without coeliac disease. Population questionnaires have shown that about 10% of noncoe...

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Both CD and NCGS subjects were largely adherent, and adherence did not differ between the groups. Gluten exposure varied greatly, and some CD and NCGS subjects reached gluten intake above 500 mg/day, which might have considerable health effects on the individual, especially in case of coeliac disease.