Gluten contamination in labelled gluten-free, naturally gluten-free and meals in food services in low-, middle- and high-income countries: a systematic review and meta-analysis.

The gluten-free diet is based on the consumption of foods without gluten, which aims to manage celiac disease. The concern of celiac patients is that these foods should be safe. However, gluten contamination can affect these foods. The objectives of this review and meta-analysis were first, to identify articles that detected gluten contamination in gluten-free foods using validated methods. Second, to quantify the overall prevalence of gluten contamination of naturally gluten-free foods, labelled gluten-free products, and meals prepared in food services. Third, to highlight the influence of the country's income and the period of study on this prevalence. The studies were identified in Scopus, Science Direct, Web of Science, PubMed, and Google Scholar. Forty articles were included according to PRISMA guidelines. The statistical meta-analysis was performed using MedCalc 19 software. The results show that in the gluten-free foods analysed, the overall prevalence of gluten contamination was estimated at 15.12% (95% CI: 9.56%-21.70%), with more than 20 mg/kg of gluten. Naturally gluten-free foods were significantly more contaminated than labelled gluten-free products and than meals in food services (28.32%; 9.52%; 4.66% respectively; p < 0.001). Moreover, it was noticed that oats were the most contaminated food. In addition, the prevalence of gluten contamination has significantly decreased over time. The majority of the studies were carried out in upper-middle-income and high-income countries, while only one study was conducted in lower-middle income countries. Therefore, it is necessary to implement preventive actions to reduce gluten contamination, ensuring safe gluten-free foods for celiac patients, including low-income countries.

Recent advancements in the sensors for food analysis to detect gluten: A mini-review [2019-2023].

People with celiac disease or gluten sensitivity may experience an immune reaction to the protein called gluten, which is present in wheat, barley, and rye. A strict gluten-free diet is the sole cure for these ailments. There are chances of food fraud about the claim of being gluten-free food items. As a result, there is a rising need for trustworthy and precise ways to identify gluten. There are many methods to detect gluten in food samples viz., enzyme-linked immunosorbent assay 1 Surface plasmon resonance (SPR), Electrochemical sensors, Fluorescence-based sensors, etc. The use of sensors is one of the most promising methods for gluten detection. For detecting gluten, a variety of sensors, including optical, electrochemical, and biosensors, have been developed with different limits of detection and sensitivity. The present review reports the recent advancements (2019-2023) in the development of sensors for gluten detection in food. We may conclude that sensitivity and limit of detection are not related to the type of sensor used (aptamer or antibody-based), however, there are advancements, with the year, on the simplicity of the material used like paper-based sensors and paradigm shift to reagent free sensors by the spectral analysis. Also, recent work shows the potential of IoT-based studies for gluten detection.

Deep-Dive Directions for Dietitians (DDDDs): a roadmap for the nutritional management of poorly responsive coeliac disease patients.

A substantial number of coeliac disease patients fail to respond to treatment with a gluten-free diet. Non-responsiveness might be multifactorial and the spectrum ranges from intentional or inadvertent gluten contamination as the main aetiology, to sensitivity to other nutrients (in addition to additives and preservatives). If the diagnosis of coeliac disease is correctly made and cross contamination and other factors have been excluded, then the aetiology behind the symptoms of a small group of coeliac patients might be refractory coeliac disease. The journey to ensure gluten contamination is not behind the persistent symptoms, is very challenging and requires in-depth training and skills. We therefore present potential guidance for the healthcare professional, in particular dietitians, on how to navigate these challenges on this journey.

Gluten Immunogenic Peptides (GIP) Point-of-Care Urine Test in Coeliac Disease Follow-up before and during the COVID-19 Lockdown in Italy.

INTRODUCTION: Celiac disease (CeD) diagnosis has worldwide shared protocols. Conversely, follow-up of patients is still an object of study. Gluten immunogenic peptide detection in the urine (GIP) appears to be a new and efficient method for dietary gluten control of patients. The present study aims to assess the clinical usefulness of the GIP point-of-care urine test in the follow-up of symptomatic and asymptomatic patients with CeD before and during the COVID-19 lockdown in Italy. METHODS: Thirty adult CeD patients on a gluten-free diet (GFD) were enrolled before and during the COVID-19 lockdown through follow-up visits or remote consultation. Patients underwent anthropometrical evaluation, dietetic interview, and State-Trait Anxiety Inventory (STAI). Then, two groups were formed: symptomatic and worried about gluten contamination. Each patient received 5 GIP point-of-care tests to perform a maximum of 5 times in the following 5 weeks in case of symptoms or anxiety state due to hypothesized gluten contamination. RESULTS: Sixteen symptomatic patients and 14 patients with concerns related to gluten contamination were included. There were no differences in age, BMI, compliance to GFD and GIP positive tests between the two groups. Worried group showed a borderline higher level of anxiety than symptomatic group (p = 0.06), with a significant minor percentage of patients reporting "no or low anxiety" (14.3% vs 50% p = 0.03). The symptomatic patients showed a higher rate of diarrhea than worried group (25% vs 0%, p = 0.04). Gluten in urine samples was globally found in 8 out of 30 cases (26.6%). CONCLUSION: The GIP test is a tool that can be used as a point of care test to assess adequate compliance with GFD and reassure symptomatic CeD patients from the feeling of anxiety for gluten contamination, especially during the COVID-19 pandemic.

Potential ways for gluten contamination of gluten-free grain and gluten-free foods: the buckwheat case.

Buckwheat has been reported to be responsible for gluten contamination in manufactured gluten-free foods (mGFFs) although it is inherently gluten-free (GF). It could happen through buckwheat grains contacting gluten-containing (GC) grains and surfaces contacted by GC grains during pre-manufacturing practices. To simulate grain contact, whole and broken GC grains (wheat, rye, barley, and oat) were mixed into buckwheat grains at the ratio of 2.5-10.0%. Grains were agitated in vessels with inner surfaces covered with buckwheat grain. Gluten was not detected in buckwheat grains contacting whole GC grains at all mixing ratios. It was not detected in the case of broken GC grains at the mixing ratio of 2.5% and oat grains at all mixing ratios. Gluten concentration increased with the increasing mixing ratio and the natural gluten concentration of broken GC grains. To simulate surface contact, GC grains were first agitated in galvanised steel vessels and then buckwheat grains were agitated together under the same conditions. Gluten was detected on galvanised steel surfaces contacted by whole and broken GC grains. It was not detected in buckwheat grains contacting the surfaces contaminated by whole GC grains. Gluten was detected in buckwheat grain in the case of the broken GC grains except for oats. Gluten concentrations increased with increasing natural gluten concentration of GC grains. Contamination of mGFFs could be linked to potential contact with buckwheat grain. This contamination issue could be resolved through regulations mandating the proof of being GF for ingredients used in the production of mGFFs.

Gluten contamination in manufactured gluten-free foods in Turkey.

Gluten contamination in manufactured gluten-free foods (mGFFs) is a major health, well-being and economic issue worldwide for both mandatory and voluntary GFF-consumers. Although scarce, a number of surveys have shown that up to 21.5 % of mGFFs in circulation in the market are contaminated with gluten. However, at the present time there is no published work reporting gluten contamination in mGFFs produced in Turkey. In this paper miscellaneous mGFFs produced in Turkey were analysed for gluten concentration (G) to fill this knowledge gap, and to compare the situation in Turkey with worldwide efforts on this issue. A total of 200 mGFFs from 8 product categories (snack, pasta, bread, cookie, cracker, farina, traditional and others), and manufactured using 7 main ingredients (cereal mixture, buckwheat, corn, rice, locust bean, potato, and others) were analysed. A significant portion of mGFFs (17.5 %) were contaminated with gluten and therefore unacceptable as being GFF. The results point to buckwheat as the main cause of this contamination. If buckwheat is excluded, the ratio of unacceptable mGFFs dramatically decreases to 6.3 % and probably to 1.8 %, which are comparable figures to those reported for other countries. Almost all countries are subjected to the same regulations on GFFs, and the problem of gluten contamination could readily be solved to a great extent if pre-market measures are mandated. Enforcing mGFF-producers to screen their raw materials and final products to detect the presence of gluten, and preventing the release of contaminated mGFFs into the market would be a practical measure in favour of all stakeholders involved in GFF-consumption.

Gluten Detection Methods and Their Critical Role in Assuring Safe Diets for Celiac Patients.

Celiac disease, wheat sensitivity, and allergy represent three different reactions, which may occur in genetically predisposed individuals on the ingestion of wheat and derived products with various manifestations. Improvements in the disease diagnostics and understanding of disease etiology unveiled that these disorders are widespread around the globe affecting about 7% of the population. The only known treatment so far is a life-long gluten-free diet, which is almost impossible to follow because of the contamination of allegedly "gluten-free" products. Accidental contamination of inherently gluten-free products could take place at any level from field to shelf because of the ubiquity of these proteins/grains. Gluten contamination of allegedly "gluten-free" products is a constant threat to celiac patients and a major health concern. Several detection procedures have been proposed to determine the level of contamination in products for celiac patients. The present article aims to review the advantages and disadvantages of different gluten detection methods, with emphasis on the recent technology that allows identification of the immunogenic-gluten peptides without the use of antibodies. The possibility to detect gluten contamination by different approaches with similar or better detection efficiency in different raw and processed foods will guarantee the safety of the foods for celiac patients.

A stepwise, 'test-all-positives' methodology to assess gluten-kernel contamination at the serving-size level in gluten-free (GF) oat production.

A step-wise, 'test-all-positive-gluten' analytical methodology has been developed and verified to assess kernel-based gluten contamination (i.e., wheat, barley and rye kernels) during gluten-free (GF) oat production. It targets GF claim compliance at the serving-size level (of a pouch or approximately 40-50g). Oat groats are collected from GF oat production following a robust attribute-based sampling plan then split into 75-g subsamples, and ground. R-Biopharm R5 sandwich ELISA R7001 is used for analysis of all the first15-g portions of the ground sample. A >20-ppm result disqualifies the production lot, while a >5 to <20-ppm result triggers complete analysis of the remaining 60-g of ground sample, analyzed in 15-g portions. If all five 15-g test results are <20ppm, and their average is <10.67ppm (since a 20-ppm contaminant in 40g of oats would dilute to 10.67ppm in 75-g), the lot is passed.

Oat safety for celiac disease patients: theoretical analysis correlates adverse symptoms in clinical studies to contaminated study oats.

Inclusion of oats in a gluten-free (GF) diet can provide whole grain nutritional benefits to celiac disease (CD) patients, but there has been debate regarding oat safety for these individuals. This is because of conflicting research findings, with inconsistencies attributed to varying CD subject's sensitivities to "pure" oats. Clinical trials to date have assumed oats provided to subjects to be lightly contaminated, if at all. This assumption is challenged here since oat's propensity to be "kernel" contaminated with gluten sources like wheat and barley has recently been shown to significantly complicate confirmation of a GF state. We therefore hypothesize that clinical studies may have inadvertently provided pill-like gluten kernels intermittently to study subjects, leading to adverse outcomes that could potentially explain inconsistencies between study conclusions. To test this theory, potential gluten contamination of oats used in a cross-section of 12 important oat feeding studies has been estimated, done according to descriptions of oats used, published contamination rates for various oat types, and study oat dosages. Expected gluten exposures were found to be at levels to elicit clinical effects in a large portion of CD patients, correlating with observed clinical reaction rates in those studies (P value = .0006). Estimated gluten doses were found insufficient, however, to affect morphological outcomes, whereas only 1 study had 1 case. Our analysis provides a new perspective with which to view oat safety study conclusions and justifies new clinical trials using today's higher-purity GF oats to settle the oat safety for CD patient debate.

Diet adherence and gluten exposure in coeliac disease and self-reported non-coeliac gluten sensitivity.

BACKGROUND/OBJECTIVES: Adherence to gluten-free diet in self reported non-coeliac gluten sensitive subjects is scarcely researched. Objectives of the study were to compare dietary adherence in coeliac disease (CD) subjects and in non-coeliac gluten sensitive (NCGS) subjects, and to estimate gluten exposure based on weighed food records and analysis of gluten content in selected food items. SUBJECTS/METHODS: Twenty-three subjects with biopsy verified CD on a gluten-free diet and 34 HLA-DQ2+ NCGS subjects on a self-instituted gluten-free diet were enrolled. The latter group was under investigation of CD. Dietary adherence was assessed by frequency questionnaire and structured forms supplied by weighed food records. For the analyses of food samples, the sandwich R5-ELISA, Ridascreen® Gliadin competitive method was used. RESULTS: There was no difference in dietary adherence between CD and NCGS subjects (83% vs 68%, p = 0.21). NCGS subjects were mainly self-educated in gluten-free diet compared to CD subjects (91% and 39%, respectively, p < 0.001). In non-adherent subjects, there was no difference in gluten exposure between CD and NCGS (10 vs 138 mg/day, p = 0.83). There was no difference in BMR-factor between CD and NCGS subjects, or between adherent and non-adherent subjects. CONCLUSIONS: 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.

Content Validation and Semantic Evaluation of a Check-List Elaborated for the Prevention of Gluten Cross-Contamination in Food Services.

Conditions associated to the consumption of gluten have emerged as a major health care concern and the treatment consists on a lifelong gluten-free diet. Providing safe food for these individuals includes adapting to safety procedures within the food chain and preventing gluten cross-contamination in gluten-free food. However, a gluten cross-contamination prevention protocol or check-list has not yet been validated. Therefore, the aim of this study was to perform the content validation and semantic evaluation of a check-list elaborated for the prevention of gluten cross-contamination in food services. The preliminary version of the check-list was elaborated based on the Brazilian resolution for food safety Collegiate Board Resolution 216 (RDC 216) and Collegiate Board Resolution 275 (RDC 275), the standard 22000 from the International Organization for Standardization (ISO 22000) and the Canadian Celiac Association Gluten-Free Certification Program documents. Seven experts with experience in the area participated in the check-list validation and semantic evaluation. The criteria used for the approval of the items, as to their importance for the prevention of gluten cross-contamination and clarity of the wording, was the achievement of a minimal of 80% of agreement between the experts (W-values ≥ 0.8). Moreover, items should have a mean ≥4 in the evaluation of importance (Likert scale from 1 to 5) and clarity (Likert scale from 0 to 5) in order to be maintained in the instrument. The final version of the check-list was composed of 84 items, divided into 12 sections. After being redesigned and re-evaluated, the items were considered important and comprehensive by the experts (both with W-values ≥ 0.89). The check-list developed was validated with respect to content and approved in the semantic evaluation.

Gluten-containing grains skew gluten assessment in oats due to sample grind non-homogeneity.

Oats are easily contaminated with gluten-rich kernels of wheat, rye and barley. These contaminants are like gluten 'pills', shown here to skew gluten analysis results. Using R-Biopharm R5 ELISA, we quantified gluten in gluten-free oatmeal servings from an in-market survey. For samples with a 5-20ppm reading on a first test, replicate analyses provided results ranging <5ppm to >160ppm. This suggests sample grinding may inadequately disperse gluten to allow a single accurate gluten assessment. To ascertain this, and characterize the distribution of 0.25-g gluten test results for kernel contaminated oats, twelve 50g samples of pure oats, each spiked with a wheat kernel, showed that 0.25g test results followed log-normal-like distributions. With this, we estimate probabilities of mis-assessment for a 'single measure/sample' relative to the <20ppm regulatory threshold, and derive an equation relating the probability of mis-assessment to sample average gluten content.

Indications and Use of the Gluten Contamination Elimination Diet for Patients with Non-Responsive Celiac Disease.

For the majority of patients diagnosed with celiac disease, once a gluten-free diet is initiated, symptoms improve within weeks and may completely resolve in months. However, up to 30% of patients may show signs, symptoms or persistent small intestinal damage after one year on a gluten-free diet. These patients require evaluation for other common GI etiologies and assessment of their celiac disease status in order to make a diagnosis and suggest treatment. Here, we propose an approach to evaluating patients with celiac disease with persistent symptoms, persistently elevated serology, and or persistent villous atrophy despite a gluten-free diet. We detail how to diagnose and distinguish between non-responsive and refractory celiac disease. Finally, we introduce the indications for use of the gluten contamination elimination diet and provide information for practitioners to implement the diet when necessary in their practice.

Persistent Intraepithelial Lymphocytosis in Celiac Patients Adhering to Gluten-Free Diet Is Not Abolished Despite a Gluten Contamination Elimination Diet.

The gluten-free diet (GFD) is the only validated treatment for celiac disease (CD), but despite strict adherence, complete mucosal recovery is rarely obtained. The aim of our study was to assess whether complete restitutio ad integrum could be achieved by adopting a restrictive diet (Gluten Contamination Elimination Diet, GCED) or may depend on time of exposure to GFD. Two cohorts of CD patients, with persisting Marsh II/Grade A lesion at duodenal biopsy after 12-18 months of GFD (early control) were identified. Patients in Cohort A were re-biopsied after a three-month GCED (GCED control) and patients in Cohort B were re-biopsied after a minimum of two years on a standard GFD subsequent to early control (late control). Ten patients in Cohort A and 19 in Cohort B completed the study protocol. There was no change in the classification of duodenal biopsies in both cohorts. The number of intraepithelial lymphocytes, TCRγδ+ (T-Cell Receptor gamma delta) T cell and eosinophils significantly decreased at GCED control (Cohort A) and at late control (Cohort B), compared to early control. Duodenal intraepithelial lymphocytosis persisting in CD patients during GFD is not eliminated by a GCED and is independent of the length of GFD. [NCT 02711696].