The Gluten-Free Diet: Testing Alternative Cereals Tolerated by Celiac Patients

A strict gluten-free diet (GFD) is the only currently available therapeutic treatment for patients with celiac disease, an autoimmune disorder of the small intestine associated with a permanent intolerance to gluten proteins. The complete elimination of gluten proteins contained in cereals from the diet is the key to celiac disease management. However, this generates numerous social and economic repercussions due to the ubiquity of gluten in foods. The research presented in this review focuses on the current status of alternative cereals and pseudocereals and their derivatives obtained by natural selection, breeding programs and transgenic or enzymatic technology, potential tolerated by celiac people. Finally, we describe several strategies for detoxification of dietary gluten. These included enzymatic cleavage of gliadin fragment by Prolyl endopeptidases (PEPs) from different organisms, degradation of toxic peptides by germinating cereal enzymes and transamidation of cereal flours. This information can be used to search for and develop cereals with the baking and nutritional qualities of toxic cereals, but which do not exacerbate this condition.     

Quantification of Accidental Gluten Contamination in the Diet of Children with Treated Celiac Disease

A strict gluten-free diet is extremely difficult to maintain. Protracted ingestion of gluten traces (>10 mg/day) is sufficient to cause significant damage in the architecture of the small intestinal mucosa in patients on treatment for celiac disease. The aim of this study was to directly measure the level of contaminating gluten in the daily diet of celiac children following a gluten-free diet. From April 2019 to December 2019, celiac disease children (2–18 years old) on a gluten-free diet for ≥6 months were offered to participate in this prospective-observational study. Patients and their caregivers were invited to provide a representative portion (about 10 g) of all meals consumed during a 24-h period. Participants were requested to weigh all ingested food and report items in a 24-h food diary. The gluten content was quantified by the R5 sandwich enzyme-linked immunosorbent assay method. Sixty-nine children completed the protocol. Overall, 12/448 (2.7%) food samples contained detectable amounts of gluten; of them, 11 contained 5–20 ppm and 1 >20 ppm. The 12 contaminated food samples belonged to 5/69 enrolled patients. In these 5 children, the daily gluten intake was well below the safety threshold of 10 mg/day. The present findings suggest that in a country characterized by high celiac disease awareness, the daily unintended exposure to gluten of treated celiac children on regular follow-up is very low; reassuringly, the presence of gluten traces did not lead to exceed the tolerable threshold of 10 mg/day of gluten intake in the gluten-free diet.     

Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide

BACKGROUND: Celiac disease is an immune-mediated enteropathy caused by the ingestion of gluten, a protein fraction found in certain cereals. Immunotoxic gluten peptides that are recalcitrant to degradation of digestive enzymes appear to trigger celiac syndromes. A 33-mer peptide from alpha-2 gliadin has been identified as a principal contributor to gluten immunotoxicity. A gluten-free diet is the usual first therapy for celiac disease patients; therefore, the characterization and quantification of the toxic portion of the gluten in foodstuffs is crucial to avoid celiac damage. OBJECTIVE: We aimed to develop immunologic assays as a novel food analysis tool for measuring cereal fractions that are immunotoxic to celiac disease patients. DESIGN: The design focused on the production of monoclonal antibodies against the gliadin 33-mer peptide and the development of enzyme-linked immunosorbent assays (ELISAs) and Western blot analysis with the use of novel antibodies. RESULTS: A sandwich ELISA method showed a detection limit for wheat, barley, and rye of <1 ppm prolamine. However, the method required a sample that was > or =1 order of magnitude greater for the detection of low-toxic oats, and there was no signal with the safe cereals maize and rice. A competitive ELISA method was also developed for detection of the toxic peptide in hydrolyzed food, which had a detection limit of <0.5 ppm gliadin. CONCLUSIONS: Both ELISAs designed for use with the toxic gliadin 33-mer peptide suggested a high correlation between the presence of the peptide and the amount of cereal that was toxic to celiac disease patients. The sensitivity was significantly higher than that of equivalent methods recognizing other gluten epitopes.     

Advances in celiac disease and gluten-free diet

Celiac disease is becoming an increasingly recognized autoimmune enteropathy caused by a permanent intolerance to gluten. Once thought to be a rare disease of childhood characterized by diarrhea, celiac disease is actually a multisystemic disorder that occurs as a result of an immune response to ingested gluten in genetically predisposed individuals. Screening studies have revealed that celiac disease is most common in asymptomatic adults in the United States. Although considerable scientific progress has been made in understanding celiac disease and in preventing or curing its manifestations, a strict gluten-free diet is the only treatment for celiac disease to date. Early diagnosis and treatment, together with regular follow-up visits with a dietitian, are necessary to ensure nutritional adequacy and to prevent malnutrition while adhering to the gluten-free diet for life. The purpose of this review is to provide clinicians with current updated information about celiac disease, its diverse clinical presentation and increased prevalence, the complex pathophysiology and strong genetic predisposition to celiac disease, and its diagnosis. This review focuses in detail on the gluten-free diet and the importance of intense expert dietary counseling for all patients with celiac disease. Recent advances in the gluten-free diet include food allergen labeling as well as the US Food and Drug Administration's proposed definition of the food-labeling term gluten-free. The gluten-free diet is complex and patients need comprehensive nutrition education from a skilled dietitian.     

The Gluten-Free Diet: Can Oats and Wheat Starch Be Part of It?

Objective and Conclusion: Uncertainty still exists about the use of oats and wheat starch as part of a gluten-free diet in patients with celiac disease (CD). This review should help to clarify the issues at hand. Whereas uncontaminated (from gluten/gliadin) oats and oats from cultivars not containing celiac-activating sequences of proline and glutamine can be used without risk of intestinal damage, wheat starch should not be used, unless it is free of gluten—that is, deglutinized—because even small amounts of gluten over time are able to induce small intestinal mucosal damage.     

Celiac disease: epidemiology, pathogenesis, diagnosis, and nutritional management.

Celiac disease (CD) is an inflammatory small intestinal disorder that can lead to severe villous atrophy, malabsorption, and malignancy. It is triggered by the gluten proteins of wheat, barley, and rye. All patients express the antigen-presenting molecules human leukocyte antigen-DQ2 (HLA-DQ2) and/or HLA-DQ8, which bind gluten peptides and thus activate destructive intestinal T cells. Patients with untreated CD have circulating IgA autoantibodies to the enzyme tissue transglutaminase (tTG), a component of endomysium. Testing for serum IgA tTG has a high predictive value. Therapy of CD is a lifelong gluten-free diet. Counseling by an expert dietitian and association with a celiac support group are important in helping the patient embark on a healthy gluten-free diet. Current research focuses on non-dietary therapies and treatment of refractory (diet-unresponsive) CD.     

The Gluten-Free Diet for Celiac Disease and Beyond

The gluten-free diet (GFD) has gained popularity beyond its main medical indication as the treatment for gluten-induced immune-mediated disorders such as celiac disease (CD), dermatitis herpetiformis, gluten ataxia, wheat allergy, and non-celiac gluten sensitivity. However, the diet carries some disadvantages such as elevated costs, nutritional deficiencies, and social and psychological barriers. The present work aims to review indications, proven benefits, and adverse events of a gluten-free diet. Close follow-up with patients following the diet is recommended. More data is needed to assess the effectiveness of the diet in managing mental and cognitive disorders and to establish a connection between the brain and gluten.     

Estimated Levels of Gluten Incidentally Present in a Canadian Gluten-Free Diet

Avoiding exposure to gluten is currently the only effective treatment for celiac disease. However, the evidence suggests that for most affected individuals, exposure to less than 10 mg/day is unlikely to cause histological changes to the intestinal mucosa. The daily diet of people with celiac disease does not rely solely on gluten-free pre-packaged foods, but also on naturally gluten-free grains (e.g., rice, buckwheat, ...) and foods with grain-derived ingredients (i.e., flour and starches) used for cooking and baking at home. The objective of this study was to estimate the level of incidental gluten potentially present in gluten-free diets from a Canadian perspective. We have conducted gluten exposure estimations from grain-containing foods and foods with grain-derived ingredients, taking into consideration the various rates of food consumption by different sex and age groups. These estimates have concluded that if gluten was present at levels not exceeding 20 ppm, exposure to gluten would remain below 10 mg per day for all age groups studied. However, in reality the level of gluten found in naturally gluten-free ingredients is not static and there may be some concerns related to the flours made from naturally gluten-free cereal grains. It was found that those containing a higher level of fiber and that are frequently used to prepare daily foods by individuals with celiac disease could be a concern. For this category of products, only the flours and starches labelled “gluten-free” should be used for home-made preparations.     

Nutrition in Patients with Lactose Malabsorption,Celiac Disease,and Related Disorders

Lactose malabsorption (LM), celiac disease (CD), non-celiac gluten sensitivity (NCGS), and irritable bowel syndrome (IBS) are conditions associated with food triggers, improvement after withdrawal, treatment with dietary restriction, and subsequent nutritional detriments. LM occurs when there is incomplete hydrolysis of lactose due to lactase deficiency and frequently produces abdominal symptoms; therefore, it can cause lactose intolerance (LI). A lactose-restricted diet is frequently recommended, although it can potentially lead to nutrient deficiencies. Furthermore, lactose is an essential component of fermentable oligo-, di-, and monosaccharides and polyols (FODMAPs) and is subsequently associated with intolerance to these compounds, especially in IBS. LM commonly presents in CD. Nutritional deficits are common in CD and can continue even on a gluten-free diet (GFD). Conditions triggered by gluten are known as gluten-related disorders (GRDs), including CD, wheat allergy, and NCGS. IBS can also be associated with a gluten sensitivity. A GFD is the treatment for CD, GRDs, and gluten sensitive IBS, although compliance with this restricted diet can be difficult. Strict dietary therapies can have a negative effect on quality of life. This review aims to provide an overview of the difficult nutritional elements of these disorders, which are critical for medical providers to recognize when managing these patients.     

Non-Celiac Gluten Sensitivity in the Context of Functional Gastrointestinal Disorders

Gluten-free diets are increasingly chosen in the Western world, even in the absence of a diagnosis of celiac disease. Around 10% of people worldwide self-report gluten-related complaints, including intestinal and extra-intestinal symptoms. In most cases, these subjects would be labeled as patients suffering from irritable bowel syndrome (IBS) who place themselves on a gluten-free diet even in the absence of celiac disease. In some instances, patients report a clear benefit by avoiding gluten from their diet and/or symptom worsening upon gluten reintroduction. This clinical entity has been termed non-celiac gluten sensitivity (NCGS). The symptoms referred by these patients are both intestinal and extra-intestinal, suggesting that similarly to functional gastrointestinal disorders, NCGS is a disorder of gut–brain interaction. It remains unclear if gluten is the only wheat component involved in NCGS. The mechanisms underlying symptom generation in NCGS remain to be fully clarified, although in the past few years, the research has significantly moved forward with new data linking NCGS to changes in gut motility, permeability and innate immunity. The diagnosis is largely based on the self-reported reaction to gluten by the patient, as there are no available biomarkers, and confirmatory double-blind challenge protocols are unfeasible in daily clinical practice. Some studies suggest that a small proportion of patients with IBS have an intolerance to gluten. However, the benefits of gluten-free or low-gluten diets in non-celiac disease-related conditions are limited, and the long-term consequences of this practice may include nutritional and gut microbiota unbalance. Here, we summarize the role of gluten in the clinical features, pathophysiology, and management of NCGS and disorders of gut–brain interaction.     

Expanded Role of a Dietitian in Monitoring a Gluten-Free Diet in Patients with Celiac Disease: Implications for Clinical Practice

Access to a registered dietitian experienced in celiac disease (CD) is still limited, and consultation when available focuses primarily on the elimination of gluten from the diet. Thus, the aim of this study was to evaluate the nutritional value of a gluten-free diet (GFD) in adult CD patients before, and one year after, the standard dietary education. The study included 72 CD patients on a GFD and 30 healthy controls. The dietary intake of both groups was assessed through a 3-day food diary, while adherence to a GFD in celiac subjects was assessed using Standardized Dietician Evaluation (SDE). Subsequently, all CD patients received detailed education on gluten sources, and 48 of them participated in a one-year follow-up. Results: Comparison with the control group showed that consumption of plant protein in CD patients was significantly lower, whereas fat and calories were higher. At baseline, only 62% of CD patients adhered to a GFD, but the standard dietary education successfully improved it. However, the nutritional value of a GFD after one year did not change, except for a reduced sodium intake. The CD subjects still did not consume enough calcium, iron, vitamin D, folic acid or fiber. In conclusion, while the standard dietary education improved GFD adherence, it did not significantly alter its nutritional value. Therefore, it is necessary to increase the role of a dietitian in the treatment of CD.     

Commercial assays to assess gluten content of gluten-free foods: why they are not created equal

A standardized method of analysis is needed to quantitatively determine the gluten content of food and provide the basis for enforcing regulations regarding use of the term gluten-free in food labeling. People with celiac disease should feel confident that foods labeled "gluten-free" have been assessed for gluten using the same "best available" methodology. The Association of Analytical Communities and the Codex Alimentarius Commission endorse different methods. Both are used by manufacturers in the United States to determine the gluten-free status of food. The sandwich omega-gliadin enzyme-linked immunosorbent assay (ELISA) is the official method of the Association of Analytical Communities. It is able to quantify native and heated gluten. It is unable to accurately detect and quantify barley prolamins, can over- or underestimate gluten content, and cannot accurately quantify hydrolyzed gluten. The sandwich R5 ELISA was endorsed by Codex for gluten determination. It is able to quantify native and heated gluten. One criticism is that it overestimates barley hordein. It also is unable to accurately quantify hydrolyzed gluten. Foods that can be reliably assessed for gluten using a validated commercially available ELISA are those contaminated with native and heated proteins from wheat, barley, and rye. The degree of confidence that can be placed in a manufacturer's assertion that a product is gluten-free is based on the assay used to determine the gluten content and the specific food analyzed.     

Evaluation of the Presence of Gluten in Beans Served at Self-Service Restaurants: A Problem for Celiac Disease Carriers

The aim of this study is to evaluate the gluten contamination in beans served in self-service restaurants. The study was conducted in self-service restaurants in Brasilia, where samples of common beans were collected and later analyzed using the ELISA technique. The results showed that 16% of the samples were contaminated by gluten and almost 45% of the restaurants showed at least one day of gluten contamination. This shows the lack of standardization of the preparation of beans, a fact that exposes celiac disease (CD) patients to great risk. Therefore, public health actions are necessary to ensure safe access to gluten-free food in order to avoid further complications related to celiac disease and improve quality of life for these individuals.     

Wheat Starch, Gliadin, and the Gluten-free Diet

Individuals with celiac disease generally are advised to follow a lifelong gluten-free diet and avoid consumption of the prolamins gliadin (wheat), secalin (rye), and hordein (barley). Although the designation of the diet as gluten free may imply that the diet contains zero gluten, this is not necessarily true. In some countries (eg, United States, Canada), the gluten-free diet is completely devoid of gluten and is based on foods such as rice and corn that are naturally gluten free. In others (eg, Scandinavia, United Kingdom), the gluten-free diet may include foods such as wheat starch that have been rendered gluten free but nonetheless contain small amounts of toxic prolamins. The discrepancy in the use of foods rendered gluten free exists because the amount of toxic prolamins that individuals with celiac disease may consume without damaging the mucosa of the small intestine is unknown. Minimal research has been conducted on the toxicity of foods rendered gluten free, and there are no definitive data about whether the small amount of prolamin found in these products is safe to consume. Nonetheless, the Codex Alimentarius Standard for gluten-free foods allows a certain amount of prolamin in foods designated gluten free, and these products have been used in many countries for several decades. Well-designed, scientifically sound studies are needed to help determine the amount of toxic prolamins, if any, that may be safely consumed by individuals with celiac disease. Until this research is conducted, dietitians in the United States should continue to advise their patients against the use of wheat starch and other foods rendered gluten free. J Am Diet Assoc. 2001; 101:1456-1459.     

New Insights into Non-Dietary Treatment in Celiac Disease: Emerging Therapeutic Options

To date, the only treatment for celiac disease (CD) consists of a strict lifelong gluten-free diet (GFD), which has numerous limitations in patients with CD. For this reason, dietary transgressions are frequent, implying intestinal damage and possible long-term complications. There is an unquestionable need for non-dietary alternatives to avoid damage by involuntary contamination or voluntary dietary transgressions. In recent years, different therapies and treatments for CD have been developed and studied based on the degradation of gluten in the intestinal lumen, regulation of the immune response, modulation of intestinal permeability, and induction of immunological tolerance. In this review, therapeutic lines for CD are evaluated with special emphasis on phase III and II clinical trials, some of which have promising results.     

Microbiota and Metabolomic Patterns in the Breast Milk of Subjects with Celiac Disease on a Gluten-Free Diet

The intestinal microbiome may trigger celiac disease (CD) in individuals with a genetic disposition when exposed to dietary gluten. Research demonstrates that nutrition during infancy is crucial to the intestinal microbiome engraftment. Very few studies to date have focused on the breast milk composition of subjects with a history of CD on a gluten-free diet. Here, we utilize a multi-omics approach with shotgun metagenomics to analyze the breast milk microbiome integrated with metabolome profiling of 36 subjects, 20 with CD on a gluten-free diet and 16 healthy controls. These analyses identified significant differences in bacterial and viral species/strains and functional pathways but no difference in metabolite abundance. Specifically, three bacterial strains with increased abundance were identified in subjects with CD on a gluten-free diet of which one (Rothia mucilaginosa) has been previously linked to autoimmune conditions. We also identified five pathways with increased abundance in subjects with CD on a gluten-free diet. We additionally found four bacterial and two viral species/strains with increased abundance in healthy controls. Overall, the differences observed in bacterial and viral species/strains and in functional pathways observed in our analysis may influence microbiome engraftment in neonates, which may impact their future clinical outcomes.     

Hydrocolloids in gluten-free breads: a review

Bread is a traditional food generally prepared from wheat flour. The main wheat component responsible for bread quality is gluten, which is an essential structure-binding protein. Although important, this protein can cause health problems in predisposed individuals, and is avoided in the diet of celiac disease patients. As diagnosis methods are improved, revealing the high incidence of gluten-intolerance in the western world, the demand for novel, nutritious and high-quality gluten-free foods also ascends. However, for the production of gluten-free breads the absence of gluten is critical and challenging in regards to the bread structure. Various gluten-free formulations have applied hydrocolloids to mimic the viscoelastic properties of gluten. They comprise a number of water-soluble polysaccharides with varied chemical structures providing a range of functional properties that make them suitable to this application. This paper reviews some actual facts about celiac disease and focuses on the reported applications of hydrocolloids in gluten-free breads.     

Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet.     

Challenges of Monitoring the Gluten-Free Diet Adherence in the Management and Follow-Up of Patients with Celiac Disease

Celiac disease (CD) is a chronic gluten-responsive immune mediated enteropathy and is treated with a gluten-free diet (GFD). However, a strict diet for life is not easy due to the ubiquitous nature of gluten. This review aims at examining available evidence on the degree of adherence to a GFD, the methods to assess it, and the barriers to its implementation. The methods for monitoring the adherence to a GFD are comprised of a dietary questionnaire, celiac serology, or clinical symptoms; however, none of these methods generate either a direct or an accurate measure of dietary adherence. A promising advancement is the development of tests that measure gluten immunogenic peptides in stools and urine. Causes of adherence/non-adherence to a GFD are numerous and multifactorial. Inadvertent dietary non-adherence is more frequent than intentional non-adherence. Cross-contamination of gluten-free products with gluten is a major cause of inadvertent non-adherence, while the limited availability, high costs, and poor quality of certified gluten-free products are responsible for intentionally breaking a GFD. Therefore, several studies in the last decade have indicated that many patients with CD who follow a GFD still have difficulty controlling their diet and, therefore, regularly consume enough gluten to trigger symptoms and damage the small intestine.     

Determination of gluten in glucose syrups

The gluten content in various glucose syrups was determined by two sandwich ELISA methods and one competitive ELISA. Different extraction solutions were used for ELISA methods. MALDI-TOF mass spectrometry and SDS-PAGE were also carried out as a complementary technique to ELISA methods. The analysis proved that glucose syrups analyzed in this work and used in many food products and gluten-free food products are safe for patients suffering from celiac disease. Four food products containing glucose syrup were analyzed with satisfactory results as well. One sample of chocolate bar has gluten content lower than the current limit for gluten-free foods. Gluten content above this limit was found in this chocolate bar after cocktail-gelatine extraction. This product is not labelled as gluten-free food. This fact shows that the analyses of gluten-free products are not simple and need more work and attention.