Update on nutritional aspects of gluten-free diet in celiac patients

A strict gluten - free diet 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. In recent years, the dramatically prompted changes in the dietary habit of an increasingly large population (celiac disease, non - celiac gluten sensitivit y and gluten allergy) has resulted in rising demands for gluten - free products. Before starting gluten - free diet, alteration in intestinal absorption capacity of celiac patients involves deficiencies of nutrients, vitamins and dietary minerals. The habitual poor gluten - free food choices in addition to inherent deficiencies in the gluten - free diet of diagnosed celiac patients may relate with dietary inadequacies. Therefore dietary assessment and counseling at the time of celiac disease diagnosis and ongoing c are are crucial as well as fortification of gluten - free foods also need to be considered. This article reviews the nutritional aspects of gluten - free diet in celiac patients and provides an up - date of dietetic recommendations to correct these deficiencies and to ensure optimum gluten - free diet compliance

Alternative grains as potential raw material for gluten– free food development in the diet of celiac and gluten– sensitive patients

Celiac disease is an autoimmune disorder resulting from gluten intolerance and is based on a genetic predisposition. Gluten is a protein composite found in the cereals wheat, rye, barley and certain oat varieties. A strict gluten-free diet is the only currently available therapeutic treatment for patients with celiac disease. Rising demands for gluten-free products parallels the apparent or real increase in celiac disease, non-celiac gluten sensitivity and gluten allergy. However, gluten removal results in major problems for bakers, and currently, many gluten-free products available on the market are of low quality exhibiting poor mouthfeel and flvor. Thus, an increasing trend in research is focusing on the application of alternative grains potentially healthy to elaborate gluten-free products. A promising area is the use of cereals (rice, corn and sorghum), minor cereals (fonio, teff, millet and job’s tears) or pseudocereals such as amaranth, buckwheat, quinoa. Nevertheless, commercialization of these products is still quite limited. The aim of this work is to review recent advances in research about the nutritional quality and potential health benefis of alternative grains tolerated by patients with gluten related pathologies.Junta de Andalucía P09AGR-478

Role of oats in celiac disease

A gluten-free diet is currently the only effective means of treating individuals with celiac disease. Such a diet enables celiac patients to control their symptoms and avoid various complications associated with this condition. However, while the quality of gluten-free foods has significantly improved during recent decades, maintenance of a gluten-free diet does not necessarily ensure adequate nutritional intake. Because oats are an important source of proteins, lipids, vitamins, minerals, and fibre, their inclusion in a gluten-free diet might improve the nutritional status of a celiac patient. Although oats are included in the list of gluten-free ingredients specified in European regulations, their safety when consumed by celiac patients remains debatable. Some studies claim that pure oats are safe for most celiac people, and contamination with other cereal sources is the main problem facing people with this disease. However, it is necessary to consider that oats include many varieties, containing various amino acid sequences and showing different immunoreactivities associated with toxic prolamins. As a result, several studies have shown that the immunogenicity of oats varies depending on the cultivar consumed. Thus, it is essential to thoroughly study the variety of oats used in a food ingredient before including it in a gluten-free diet

Biomarkers to monitor gluten-free diet compliance in celiac patients

Gluten-free diet (GFD) is the only treatment for celiac disease (CD). There is a general consensus that strict GFD adherence in CD patients leads to full clinical and histological remission accompanied by improvement in quality of life and reduced long-term complications. Despite the importance of monitoring the GFD, there are no clear guidelines for assessing the outcome or for exploring its adherence. Available methods are insufficiently accurate to identify occasional gluten exposure that may cause intestinal mucosal damage. Serological tests are highly sensitive and specific for diagnosis, but do not predict recovery and are not useful for follow-up. The use of serial endoscopies, it is invasive and impractical for frequent monitoring, and dietary interview can be subjective. Therefore, the detection of gluten immunogenic peptides (GIP) in feces and urine have been proposed as new non-invasive biomarkers to detect gluten intake and verify GFD compliance in CD patients. These simple immunoassays in human samples could overcome some key unresolved scientific and clinical problems in CD management. It is a significant advance that opens up new possibilities for the clinicians to evaluate the CD treatment, GFD compliance, and improvement in the quality of life of CD patient

Fecal Gluten Peptides Reveal Limitations of Serological Tests and Food Questionnaires for Monitoring Gluten-Free Diet in Celiac Disease Patients

Objectives: Treatment for celiac disease (CD) is a lifelong strict gluten-free diet (GFD). Patients should be followed-up with dietary interviews and serology as CD markers to ensure adherence to the diet. However, none of these methods offer an accurate measure of dietary compliance. Our aim was to evaluate the measurement of gluten immunogenic peptides (GIP) in stools as a marker of GFD adherence in CD patients and compare it with traditional methods of GFD monitoring. Methods: We performed a prospective, nonrandomized, multicenter study including 188 CD patients on GFD and 84 healthy controls. Subjects were given a dietary questionnaire and fecal GIP quantified by enzyme-linked immunosorbent assay (ELISA). Serological anti-tissue transglutaminase (anti-tTG) IgA and anti-deamidated gliadin peptide (anti-DGP) IgA antibodies were measured simultaneously. Results: Of the 188 celiac patients, 56 (29.8%) had detectable GIP levels in stools. There was significant association between age and GIP in stools that revealed increasing dietary transgressions with advancing age (39.2% in subjects ≥13 years old) and with gender in certain age groups (60% in men ≥13 years old). No association was found between fecal GIP and dietary questionnaire or anti-tTG antibodies. However, association was detected between GIP and anti-DGP antibodies, although 46 of the 53 GIP stool-positive patients were negative for anti-DGP. Conclusions: Detection of gluten peptides in stools reveals limitations of traditional methods for monitoring GFD in celiac patients. The GIP ELISA enables direct and quantitative assessment of gluten exposure early after ingestion and could aid in the diagnosis and clinical management of nonresponsive CD and refractory CD. Trial registration number NCT02711397

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 nu-merous 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.Junta de Andalucía AT17_5489_USE, PI-0053-201

Stimulatory Response of Celiac Disease Peripheral Blood Mononuclear Cells Induced by RNAi Wheat Lines Differing in Grain Protein Composition

Wheat gluten proteins are responsible for the bread-making properties of the dough but also for triggering important gastrointestinal disorders. Celiac disease (CD) affects approximately 1% of the population in Western countries. The only treatment available is the strict avoidance of gluten in the diet. Interference RNA (RNAi) is an excellent approach for the down-regulation of genes coding for immunogenic proteins related to celiac disease, providing an alternative for the development of cereals suitable for CD patients. In the present work, we report a comparative study of the stimulatory capacity of seven low-gluten RNAi lines differing in grain gluten and non-gluten protein composition, relevant for CD and other gluten pathologies. Peripheral blood mononuclear cells (PBMCs) of 35 patients with active CD were included in this study to assess the stimulatory response induced by protein extracts from the RNAi lines. Analysis of the proliferative response and interferon-gamma (INF-γ) release of PBMCs demonstrated impaired stimulation in response to all RNAi lines. The lower response was provided by lines with a very low content of α- and γ-gliadins, and low or almost devoid of DQ2.5 and p31–43 α-gliadin epitopes. The non-gluten protein seems not to play a key role in PBMC stimulation.Spanish Ministry of Economy, Industry and competitiveness AGL2016-80566-PEuropean Regional Development Fund (FEDER

Celiac Immunogenic Potential of α-Gliadin Epitope Variants from Triticum and Aegilops Species

The high global demand of wheat and its subsequent consumption arise from the physicochemical properties of bread dough and its contribution to the protein intake in the human diet. Gluten is the main structural complex of wheat proteins and subjects affected by celiac disease (CD) cannot tolerate gluten protein. Within gluten proteins, α-gliadins constitute the most immunogenic fraction since they contain the main T-cell stimulating epitopes (DQ2.5-glia-α1, DQ2.5-glia-α2, and DQ2.5-glia-α3). In this work, the celiac immunotoxic potential of α-gliadins was studied within Triticeae: diploid, tetraploid, and hexaploid species. The abundance and immunostimulatory capacity of CD canonical epitopes and variants (with one or two mismatches) in all α-gliadin sequences were determined. The results showed that the canonical epitopes DQ2.5-glia-α1 and DQ2.5-glia-α3 were more frequent than DQ2.5-glia-α2. A higher abundance of canonical DQ2.5-glia-α1 epitope was found to be associated with genomes of the BBAADD, AA, and DD types; however, the abundance of DQ2.5-glia-α3 epitope variants was very high in BBAADD and BBAA wheat despite their low abundance in the canonical epitope. The most abundant substitution was that of proline to serine, which was disposed mainly on the three canonical DQ2.5 domains on position 8. Interestingly, our results demonstrated that the natural introduction of Q to H at any position eliminates the toxicity of the three T-cell epitopes in the α-gliadins. The results provided a rational approach for the introduction of natural amino acid substitutions to eliminate the toxicity of three T-cell epitopes, while maintaining the technological properties of commercial wheats

The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.España, MINECO Projects AGL2013-48946-C3-1-R, AGL2013-48946-C and AGL2016-80566-