Lifelong Gluten-free Diet Research Articles

Modern methods for estimation of dietary adherence and quality of life for patients with coeliac disease

Rationale: Coeliac disease (CD) impacts health-related quality of life (QOL) due to the requirement to follow a strict lifelong gluten free diet, a number of nutritional deficiencies and clinical manifestations of CD. The aim of our study is to monitor the dietary adherence and to estimate QOL in patients with CD using translated questionnaires.

Gluten-Free Bread from ingredients and nutrition point of view: A Mini-Review

Consistent gluten consumption leads to one of the most prevalent immune-mediated disorders i.e. celiac disease (CD). Gluten derived from wheat, rye and barley exhibit antigenic properties that may promote immune reactions in some receptive individuals. Hence, a life-long gluten-free diet (GFD) is being recommended as the best therapeutic treatment. Nevertheless, several research fonts have revealed that gluten-free (GF) products play a vital role in the diet, but bakery goods, especially gluten-free bread (GFB) indicate technological challenges and demonstrate sensory, nutritional and quality imbalances. To overcome these issues, numerous investigations such as raw materials or processing technologies are being carried out. To the best of our knowledge, to date no permanent solution has been evolved for replacing the gluten completely, though the combination of certain ingredients, additives and technologies are providing promising results, keeping the door open for further improvements. This review aims to collect recent information on approaches, improvements and still existing gaps in GF bread making.

Negative predictive value of the repeated absence of gluten immunogenic peptides in the urine of treated celiac patients in predicting mucosal healing: new proposals for follow-up in celiac disease

The treatment of celiac disease (CD) is a lifelong gluten-free diet (GFD). The current methods for monitoring GFD conformance, such as a dietary questionnaire or serology tests, may be inaccurate in detecting dietary transgressions, and duodenal biopsies are invasive, expensive, and not a routine monitoring technique. Our aim was to determine the clinical usefulness of urine gluten immunogenic peptides (GIP) as a biomarker monitoring GFD adherence in celiac patients and to evaluate the concordance of the results with the degree of mucosal damage. A prospective observational study was conducted involving 22 de novo CD patients, 77 celiac patients consuming a GFD, and 13 nonceliac subjects. On 3 d of the week, urine samples were collected and the GIP concentrations were tested. Simultaneously, anti-tissue transglutaminase antibodies, questionnaire results, clinical manifestations, and histological findings were analyzed. Approximately 24% (18 of 76) of the celiac patients consuming a GFD exhibited Marsh II-III mucosal damage. Among this population, 94% (17 of 18) had detectable urine GIP; however, between 60% and 80% were asymptomatic and exhibited negative serology and appropriate GFD adherence based on the questionnaire. In contrast, 97% (31 of 32) of the celiac patients without duodenal damage had no detectable GIP. These results demonstrated the high sensitivity (94%) and negative predictive value (97%) of GIP measurements in relation to duodenal biopsy findings. In the de novo CD-diagnosed cohort, 82% (18 of 22) of patients had measurable amounts of GIP in the urine. Determining GIP concentrations in several urine samples may be an especially convenient approach to assess recent gluten exposure in celiac patients and appears to accurately predict the absence of histological lesions. The introduction of GIP testing as an assessment technique for GFD adherence may help in ascertaining dietary compliance and to target the most suitable intervention during follow-up.

Pilot scale production of a non-immunogenic soluble gluten by wheat flour transamidation with applications in food processing for celiac-susceptible people

Celiac disease (CD) is an immune-mediated disease triggered by wheat gluten and related prolamins. A lifelong gluten-free (GF) diet is mandatory to normalize the intestinal mucosa. We previously found that transamidation by microbial transglutaminase of gluten was effective in suppressing the gliadin-specific inflammatory response in CD patients without influencing the main technological properties of wheat flour or semolina. In this study, we produced on a pilot scale a soluble form of transamidated gluten (soluble protein fraction, spf), characterised by a high protein content (88 mg/ml), while native gluten was dramatically reduced (32 ± 2 ppm; R5-ELISA). Using HLA-DQ8 transgenic mice as a CD model, we found suppression of interferon-γ secretion in gliadin-specific CD4+ T cells challenged with spf-primed dendritic cells. In terms of functional properties, spf showed both solubility and emulsifying activity values within the range of commercial soluble glutens. Notably, dough prepared by mixing rice flour with spf could leaven. After baking, blended rice bread had a higher specific volume (2.9 ± 0.1) than control rice bread (2.0 ± 0.1) and acquired wheat-like sensory features. Taken together, our results highlighted the technological value of transamidated soluble gluten to improve both nutritional and sensory parameters of GF food.

Teaching Families of Children with Celiac Disease about Gluten-Free Diet Using Distributed Education: a Pilot Study.

Introduction: Treatment of celiac disease is a strict life-long gluten-free diet (GFD). The GFD is complex, and counseling by a dietitian is essential. The number of new referrals for GFD education has increased. We studied the feasibility of GFD teaching using distributed education.Methods: The IWK Health Center in Halifax is the only tertiary-care pediatric hospital in the 3 Maritime provinces with GFD experienced dietitians. Families travel long distances to attend teaching sessions. Families outside the Halifax area were offered to participate in the 2.5-hour education sessions held once a month via live videoconference link at their regional hospitals. All participants were surveyed with a 10-item questionnaire assessing the content and delivery and usefulness of information.Results: Over a 6-month period, 39 families attended the sessions, 21 locally and 18 at distributed sites across the Maritimes. The survey was completed by 26 participants (67%). All participants at both sites strongly agreed or agreed that their setting was good for learning and the information provided was easy to understand. There were no significant differences between the 2 groups on any individual questions in the 2 domains assessed (all P > 0.06).Conclusions: Distributed education on GFD is feasible and as effective as in person education. It affords convenience and savings to families by reducing travel costs.

Difficulties Assessing Adherence to Gluten-free Diet in Celiac Patients

To date the only efficient treatment of celiac disease is a lifelong gluten-free diet (GFD), which involves relevant lifestyle changes. Numerous methods measure adherence to GFD, but none is completely reliable. The aim of the study was to compare three frequently used methods to measure adherence to GFD and study factors that influence adherence to GFD. Eighty-one celiac patients 15 years or older, on GFD were evaluated by dietitian interview, a Celiac Dietary Adherence Test (CDAT) and blood antitransglutaminase antibodies (tTG). Factors influencing adherence were assessed by an ad-hoc questionnaire following WHO criteria. Adherent and non-adherent patients were classified in the same category in 44.4% of cases (n=36), (non-adherent=35.8% and adherent= 8.6%). In general, methods identified better non-adherent than adherent individuals. Among the 5 realms defined by WHO, when tTG (positive/negative) defined adherence, logistic regression identified ten significant variables (information about disease, income, education, cost of gluten-free products, eating in restaurants, time on GFD, symptoms at diagnosis, number of symptoms at time of diagnosis, other chronic diseases present, allergy/food intolerance plus a chronic disease and CD). Using the interview as reference, two variables were significant (self-perception of knowledge of the GFD, and presence of gastrointestinal symptoms when gluten is consumed). Results illustrate the difficulties of measuring both adherence to GFD and the factors that influences it. Further studies should explore new markers able to measure the amount of gluten necessary to activate autoantibodies production and the time they take to stop their production once the patient stops gluten ingestion.

Should the Glu Be Ten or Twenty? An Update on the Ongoing Debate on Gluten Safety Limits for Patients with Celiac Disease

The only currently accepted and recommended treatment for individuals diagnosed with celiac disease (CD) is a strict life-long gluten-free diet (GFD). While the use of the GFD is well-established, strict adherence to diet is not easy to accomplish. In addition, the administration of a GFD may be compromised by inadvertent exposure to small amounts of gluten. International guidelines define a gluten-free product as one containing less than 20 parts per million (ppm), (20 milligrams of gluten per 1 kg of food) gluten. A number of reports have assessed the safe upper limit for gluten exposure for patients with CD, with general consensus that patients with CD should limit their daily intake to less than 50 mg.

X6: A Novel Antibody for Potential Use in Gluten Quantification.

Gliadin is a fraction of gluten, known to trigger celiac disease in susceptible people. To date, the life-long gluten-free diet is used for the prevention of this disease. Hence, methods for gluten control in foods are of significant importance. Being one of the most-used methods used for this purpose, ELISA should use high-affinity antibodies to gliadin peptides involved into celiac process. This study investigates the characteristics of a novel anti-gliadin antibody X6. We found the QXQPFPXP site to be a recognized epitope that provides specific binding of the antibody to cereal prolamins involved in celiac disease manifestation. A specificity study using immunoblotting shows the recognition of wheat, barley and rye proteins—as well as α-gliadin homologs from non-edible cereals (Dasypyrum villosum). Reactivity to avenin was less pronounced, as this protein does not contain the PFP motif most critical for antibody recognition. The proteins of Zea mays and Setaria italica were not recognized by X6. X6-based ELISA highly correlated with R5 and G12, which are Codex Alimentarius standards in the quantitative assessment of gluten content (Pearson’s R = 0.86 and 0.87, respectively). Qualitative assessment revealed no significant differences between R5 and G12 and X6.

Further Steps Toward the Development of Gluten Reference Materials - Wheat Flours or Protein Isolates?

Celiac disease is a gluten-induced hypersensitivity reaction that requires a lifelong gluten-free diet. Gluten-free foods must not contain more than 20 mg/kg gluten as laid down by Codex Alimentarius. Measuring the presence of gluten with routine immunoanalytical methods in food is a serious challenge as many factors affect accurate determination. Comparability of the results obtained with different methods and method validation are hindered by the lack of a widely accepted reference material (RM). The core questions of RM development from wheat are the number of cultivars to be included and the format of gluten (i.e., flour, gluten, or gliadin isolates) to be applied. Therefore, the aim of our work was to produce an appropriate gluten RM from wheat. For this, five previously selected wheat cultivars and their blend were used to produce flours, gluten and gliadin isolates under laboratory conditions. Protein content, protein composition and responses to different ELISA methods were compared and widely evaluated in our study. The protein contents of the flours were 12.1–18.7%, those of the gluten isolates 93.8–97.4% and those of the gliadin isolates 72.7–101.9%. The gluten and gliadin isolates had similar protein profiles as the source flours. By comparing the different wheat cultivars and their protein isolates, we found that the isolation had a smaller effect on protein composition than genetic variability. The choice of a blend would be more suitable for the production of a RM in case of flours and also isolates. The immunoanalytical results showed that the isolation had an effect on the analytical results, but its extent depended on the ELISA method. The use of flour would be more applicable in this regard, but handling of the material and long-term stability should also be considered in the final decision of gluten RM production.

The Remember/Regeneration Therapy Method as a New Holistic Approach for Celiac Disease: Two Case Reports

Background: celiac disease (cd) is a widespread disorder caused by an intolerance to gluten which is a protein found in many foods in genetically susceptible individuals. The disease is characterized by small-intestinal mucosal injury and nutrient malabsorption. Currently, in spite of a life-long gluten-free diet is the effective and available treatment option for patients with CD, the widespread use of wheat-derived gluten in the food industry limits the effectiveness of treatment. Therefore, it is needed to perform further studies on nondietary therapies which solve the causes of the disease. The Remember/Regeneration Therapy Method (RTM) is a novel holistic medicine approach that targets physiopathological changes in quadruplet body structures and includes various complementary methods such as acupuncture, ozone therapy, and phytotherapy, etc. in different combinations which are determined depending on the disease.

SENSORIAL ACCEPTABILITY OF GLUTEN FREE MALAYSIAN TRADITIONAL KUIH FROM LEFTOVER COCONUT PULP FLOUR FLOUR

Gluten is a protein found in cereals, giving foods a pleasant elasticity and body structure. Cereal products, containing gluten are rich in dietary fibre. Although gluten plays a vital role in food production, it is harmful to gluten intolerant people (GIP). Hence, GIP is forced to follow a lifelong gluten-free diet, affecting their dietary fibre intake, essential against diarrhoea, constipation and colon cancer. Coconut (Cocos Nucifera) is the largest local commodity after rice in Malaysia. Coconut meat is usually processed for coconut water, coconut milk and coconut oil, while the leftover coconut pulp (LOCP) is disposed or used for livestock feeding. However, this LOCP is rich in dietary fibre and gluten-free, making it the best alternative for making gluten-free Malaysian Traditional Kuih (MTK), suitable for GIP. Apam Balik Kuih (ABK) is a highly popular MTK. Therefore, this study focused on providing gluten-free MTK from leftover coconut pulp flour (LOCPF), high in dietary fibre and consisting of three formulations; 60% LOCPF and 40% rice flour (F2), 100% LOCPF (F3) and a control sample from 100% wheat flour (F1). Two sensorial evaluations were conducted (semi-trained panel and consumer acceptability). The semi-trained panel showed similar results for appearance, texture, and mouthfeel for all variants of all, F3 was rated as unpleasant tasting. F1 was graded medium brown, while F2 and F3 were graded brown in colour. F2 was rated as the best for overall acceptability. For consumer acceptability, F1 rated “slightly like” in all criteria. F2 rated “neutral” for colour, texture, mouthfeel and “slightly like” for appearance, taste and overall acceptability. F3 rated “neutral” in all criteria. Among all, F2 showcased the best formulation as depicted by higher mean score rated. Based on these results, LOCPF proved a good gluten-free alternative flour with high fibre content, beneficial for pharmaceutical and food industry application.

An Overview of International Guidelines Focusing on the Long-Term Management of Coeliac Disease

Coeliac disease (CD) is an autoimmune disorder characterised by, but not isolated to, intestinal enteropathy in response to exposure to gluten in predisposed individuals. The mainstay of the management of CD is a strict, lifelong gluten free diet (GFD). Although numerous publications have focused on pathways to guide the diagnosis of CD, recommendations for the care of patients after diagnosis are less well established. This manuscript aimed to review the available published guidelines focusing on the ongoing management and follow-up of patients after diagnosis with CD and commencement of a GFD. All available guidelines recommend strict adherence to a GFD with most recommending an annual review by a specialist clinician, focusing on symptoms, adherence and growth. In addition to monitoring micronutrient status, some guidelines suggest monitoring bone mineral density in at-risk groups and screening for other autoimmune disorders. The benefit of multi-disciplinary input was outlined in many guidelines, in particular, the involvement of a specialist dietitian to provide nutritional counselling and support. While the available guidelines provide key messages, they highlight a lack of strong evidence and some inconsistences. Further evidence is required to support high quality, best-practice management strategies that will optimise the outcomes of patients with CD.

COVID-19 pandemic perception in adults with celiac disease: an impulse to implement the use of telemedicine

BackgroundCoronavirus Disease 2019 (COVID-19) causes severe complications and deaths all over the world. COVID-19 also has indirect effects from the lockdown and the possible lack of food. We aimed to evaluate the perception of this in Celiac Disease (CeD) patients who require a lifelong gluten-free diet as a therapy. MethodsWe invited by e-mail CeD adult patients from the University of Salerno (Campania, South Italy) and the University of Padua (Veneto, North Italy) to answer an ad hoc COVID-19 survey. ResultsWe sent the web survey to 651 email addresses and we received 276 answers (42,4%). CeD patients did not feel more vulnerable because they had CeD (not at all 56.6%) and they did not worry much about the possible shortness of gluten-free food during the epidemic (not at all 48.5%). The most worried were the elderly patients, patients with other comorbidities and females. Finally, CeD patients were happy with remote consultations and explicitly asked to have them. DiscussionThe COVID-19 pandemic has impacted a proportion of patients with CeD; in particular, women, elderly patients, patients with other comorbidities. COVID-19, although a challenging experience from the medical and the psychological point of view, has offered an opportunity to practice, on a large-scale, a remote consultation approach for CeD healthcare.

Evaluating the Dietary Intakes of Energy, Macronutrients, Sugar, Fiber, and Micronutrients in Children With Celiac Disease.

Children with celiac disease (CD) follow a lifelong gluten-free diet. This restrictive diet may be associated with nutritional compromise. Our objectives were, therefore, to evaluate the dietary composition (energy, macronutrients and micronutrients, and fiber) in children with CD compared with healthy controls (HC) and relationship between dietary composition and socioeconomic status. This cross-sectional, case-control study recruited children with CD ages 2 to 18 years and HC matched for age, sex, and socioeconomic status. Clinical, sociodemographic, and dietary information were collected. A false discovery rate correction was applied to the P-value for multiple comparisons (q-value). Sixty-five CD children were matched with 65 HC (mean [SD] age: 10.2 [3.6] vs 10.1 [3.7] years, P = 0.96). Compared with HC, CD children had higher intakes of energy (2413.2 [489.9] vs 2190.8 (593.5) kcal/day, P = 0.02), total fat (818.1 ± 180.9 vs 714.3 ± 212.2 kcal/day, q = 0.018), and subtypes of fat (saturated, polyunsaturated, and monounsaturated). There were no differences in other macronutrients, sugar, micronutrients, or fiber between CD and HC, and no difference in dietary intake among CD between socioeconomic disadvantage versus advantage. Children with CD had lower weight z-scores (-0.06 [1.05] vs 0.47 [0.96], P = 0.003) and body mass index (BMI) z-scores (-0.02 [0.88] vs 0.41 [1.09], P = 0.02) than HC. Children with CD had higher calorie and fat intake compared with HC. Despite this, CD children had lower weight and BMI z-scores compared with HC.

Celiac disease: a multi-faceted medical condition.

Celiac disease (CD) is a systemic condition of autoimmune origin, affecting genetically predisposed individuals who at some point lose tolerance towards dietary gluten. Prevalence in the general population is 0.5 - 1%, with a higher frequency in women. The most important environmental factor for CD is ingestion of specific gluten peptides. It triggers a sequence of molecular events, involving the intestinal permeability and the immune system, which ends in damage of the intestinal mucosa. A number of studies have demonstrated the correlation between the intestinal microbiota and celiac disease. MicroRNAs through their regulatory role on gene expression have been implicated in the pathogenesis of CD and suggested as potential biomarkers. In the pediatric and adult population, CD displays different clusters of clinical symptoms. Persistent diarrhea, abdominal pain and involuntary weight loss are the classic symptoms of CD. In the majority of cases diagnosis relies on the combination of serum autoantibodies (anti-transglutaminase and anti-endomisium IgA) and duodenal biopsy showing villous atrophy, crypt hyperplasia and intraepithelial lymphocytes. Observance of a lifelong gluten-free diet, which interrupts the immune response to gluten peptides, is the only effective treatment of CD.

CRISPR/Cas9 Gene Editing of Gluten in Wheat to Reduce Gluten Content and Exposure-Reviewing Methods to Screen for Coeliac Safety.

Ingestion of gluten proteins (gliadins and glutenins) from wheat, barley and rye can cause coeliac disease (CD) in genetically predisposed individuals. The only remedy is a strict and lifelong gluten-free diet. There is a growing desire for coeliac-safe, whole-grain wheat-based products, as consumption of whole-grain foods reduces the risk of chronic diseases. However, due to the large number of gluten genes and the complexity of the wheat genome, wheat that is coeliac-safe but retains baking quality cannot be produced by conventional breeding alone. CD is triggered by immunogenic epitopes, notably those present in α-, γ-, and ω-gliadins. RNA interference (RNAi) silencing has been used to down-regulate gliadin families. Recently, targeted gene editing using CRISPR/Cas9 has been applied to gliadins. These methods produce offspring with silenced, deleted, and/or edited gliadins, that overall may reduce the exposure of patients to CD epitopes. Here we review methods to efficiently screen and select the lines from gliadin gene editing programs for CD epitopes at the DNA and protein level, for baking quality, and ultimately in clinical trials. The application of gene editing for the production of coeliac-safe wheat is further considered within the context of food production and in view of current national and international regulatory frameworks.

The Long-Term Safety and Quality of Life Effects of Oats in Dermatitis Herpetiformis.

The treatment of choice for dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is a life-long gluten-free diet (GFD). In a GFD, wheat, rye and barley should be strictly avoided, but the role of oats is more controversial. This study aimed to investigate the safety and long-term quality of life and health effects of oat consumption in 312 long-term treated DH patients. Baseline data were gathered from patient records and follow-up data from questionnaires or interviews, and validated questionnaires were used to assess quality of life. We found that altogether 256 patients (82%) were consuming oats as part of their GFD at the follow-up. Long-term follow-up data showed that there were no differences in the presence of long-term illnesses, coeliac disease complications or the usage of medication between those consuming and not consuming oats. However, oat consumers had a better quality of life and reported ongoing gastrointestinal symptoms less frequently (4% vs 19%, p = 0.004) at the follow-up than those not consuming oats. The study established that oats are safe for DH patients and in the long-term seem to improve the quality of life of DH patients.

Celiakie dospělých

Celiac disease is a lifelong autoimmune disorder that occurs in genetically predisposed people when consuming gluten. Its prevalence is around 1% of the population with about twice higher proportion of women. Celiac disease is one of the most common causes of malabsorption, however, its manifestations can be quite diverse - from completely asymptomatic to fully developed malabsorption syndrome. Extraintestinal manifestations are a common finding in adults. The gold standard of diagnosis is the serological detection of specific antibodies (the serum tissue transglutaminase IgA antibodies) in combination with a typical histological finding from a duodenal biopsy. Causal treatment is a lifelong gluten-free diet. Strict adherence to gluten-free diet will reduce the risk of serious complications (intestinal T-cell lymphoma). In the following case report we present a case of a 58-year-old patient, who have been diagnosed with celiac disease at this age based on non-classical symptoms. Specifically, these were multiple pathological fractures from metabolic bone disease due to malabsorption of calcium and vitamin D and subsequent secondary hyperparathyroidism.

Natural variants of α-gliadin peptides within wheat proteins with reduced toxicity in coeliac disease.

The only generally accepted treatment of coeliac disease (CD) is a lifelong gluten-free diet. Wheat gluten proteins include gliadins, low and high molecular weight glutenins. However, we have found significant structural variations within these protein families among different cultivars. To determine which structural motifs might be less toxic than others, we assessed five variants of α-gliadin immunodominant CD-toxic peptides synthesised as 16mers in CD T cell stimulation assays with gluten-sensitive T cell lines generated from duodenal biopsies from CD-affected individuals. The peptides harboured the overlapping T cell epitopes DQ 2.5-glia-α-2 and naturally occurring variants that differed in certain amino acids (AA). The results revealed that introduction of two selected AA substitutions in α-gliadin peptides reduced immunogenicity. A peptide with three AA substitutions involving two glutamic acids (E) and one glutamine residue (G) revealed the peptide was negative in 5:5 samples. We used CD small-intestinal organ culture to assess CD toxicity that revealed two peptides with selected substitution of both glutamic acid (E) and proline (P) residues abrogated evidence of CD toxicity.

Intestinal TG3- and TG2-Specific Plasma Cell Responses in Dermatitis Herpetiformis Patients Undergoing a Gluten Challenge.

Dermatitis herpetiformis (DH), a cutaneous manifestation of coeliac disease, is characterized by transglutaminase (TG) 3-targeted dermal immunoglobulin A (IgA) deposits. The treatment for DH is the same as for coeliac disease, namely a life-long gluten-free diet. DH patients typically have gluten-dependent circulating autoantibodies targeting TG3 and TG2, and plasma cells secreting such autoantibodies have been detected in the small intestinal mucosa. This study investigates the gluten-responsiveness of intestinal TG3 and TG2 antibody-secreting plasma cells in 16 treated DH patients undergoing a gluten challenge. The frequency of both plasma cell populations increased significantly during the challenge, and their frequency correlated with the corresponding serum autoantibody levels at post-challenge. TG3-specific plasma cells were absent in all 18 untreated coeliac disease patients and seven non-coeliac control subjects on gluten-containing diets. These findings indicate that, in DH, both intestinal TG3- and TG2-antibody secreting plasma cells are gluten-dependent, and that TG3-antibody secreting plasma cells are DH-specific.