Gliadin proteolytical resistant peptides: the interplay between structure and self-assembly in gluten-related disorders.
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ABSTRACT:
SUBMITTER: Herrera MG
PROVIDER: S-EPMC8724473 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Background. Celiac disease seems to be rare in Colombians, but there are currently no data about the prevalence rates of symptomatic adverse reactions to gluten or adherence to gluten-free diet (GFD) in this population. Aim. to evaluate the self-reported prevalence rates of adverse reactions to gluten, adherence to GFD, and gluten-related disorders at population level in Colombia. Methods. A self-administered questionnaire-based cross-sectional study was conducted in a population from Northwest Colombia. Results. The estimated prevalence rates were (95% CI) 7.9% (6.5-9.6) and 5.3% (4.1-6.7) for adverse and recurrent adverse reactions to wheat/gluten, respectively, adherence to GFD 5.9% (4.7-7.4), wheat allergy 0.74% (0.3-1.4), and nonceliac gluten sensitivity 4.5% (3.5-5.8). There were no self-reported cases of celiac disease. Prevalence of self-reported physician-diagnosis of gluten-related disorders was 0.41% (0.17-0.96). Most respondents reported adherence to GFD without a physician-diagnosis of gluten-related disorders (97.2%). The proportion of gluten avoiders was 17.2% (15.2-19.5). Most of them did not report recurrent adverse reactions to wheat/gluten (87.0%). Conclusions. Nonceliac gluten sensitivity is rarely formally diagnosed in Colombia, but this population has the highest prevalence rate of adherence to GFD reported to date. Consequently, most respondents were avoiding wheat- and/or gluten-based products for reasons other than health-related symptoms.
| S-EPMC5018322 | biostudies-other
Project description:Wheat flour cannot be tolerated by those who suffer allergies to gluten. Human pathologies associated with grain proteins have increased worldwide in recent years, and the only effective treatment available is a lifelong gluten-free diet, which is complicated to follow and detrimental to gut health. This manuscript describes the development of wheat bread potentially suitable for celiac patients and other gluten-intolerant individuals. We have made bread using wheat flour with very low content of the specific gluten proteins (near gliadin-free) that are the causal agents for pathologies such as celiac disease. Loaves were compared with normal wheat breads and rice bread. Organoleptic, nutritional, and immunotoxic properties were studied. The reduced-gliadin breads showed baking and sensory properties, and overall acceptance, similar to those of normal flour, but with up to 97% lower gliadin content. Moreover, the low-gliadin flour has improved nutritional properties since its lysine content is significantly higher than that of normal flour. Conservative estimates indicate that celiac patients could safely consume 67 grams of bread per day that is made with low-gliadin flour. However, additional studies, such as feeding trials with gluten-intolerant patients, are still needed in order to determine whether or not the product can be consumed by the general celiac population, as well as the actual tolerated amount that can be safely ingested. The results presented here offer a major opportunity to improve the quality of life for millions of sufferers of gluten intolerance throughout the world.
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Project description:Gluten-related disorders are a complex group of diseases that involve the activation of the immune system triggered by the ingestion of gluten. Among these, celiac disease, with a prevalence of 1 %, is the most investigated, but recently, a new pathology, named nonceliac gluten sensitivity, was reported with a general prevalence of 7 %. Finally, there other less-prevalent gluten-related diseases such as wheat allergy, gluten ataxia, and dermatitis herpetiformis (with an overall prevalence of less than 0.1 %). As mentioned, the common molecular trigger is gluten, a complex mixture of storage proteins present in wheat, barley, and a variety of oats that are not fully degraded by humans. The most-studied protein related to disease is gliadin, present in wheat, which possesses in its sequence many pathological fragments. Despite a lot of effort to treat these disorders, the only effective method is a long-life gluten-free diet. This Review summarizes the actual knowledge of gluten-related disorders from a translational chemistry point of view. We discuss what is currently known from the literature about the interaction of gluten with the gut and the critical host responses it evokes and, finally, connect them to our current and novel molecular understanding of the supramolecular organization of gliadin and the 33-mer gliadin peptide fragment under physiological conditions.
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Project description:Gluten-related disorders include distinct disease entities, namely celiac disease, wheat-associated allergy and non-celiac gluten/wheat sensitivity. Despite having in common the contact of the gastrointestinal mucosa with components of wheat and other cereals as a causative factor, these clinical entities have distinct pathophysiological pathways. In celiac disease, a T-cell mediate immune reaction triggered by gluten ingestion is central in the pathogenesis of the enteropathy, while wheat allergy develops as a rapid immunoglobulin E- or non-immunoglobulin E-mediated immune response. In non-celiac wheat sensitivity, classical adaptive immune responses are not involved. Instead, recent research has revealed that an innate immune response to a yet-to-be-defined antigen, as well as the gut microbiota, are pivotal in the development in this disorder. Although impairment of the epithelial barrier has been described in all three clinical conditions, its role as a potential pathogenetic co-factor, specifically in celiac disease and non-celiac wheat sensitivity, is still a matter of investigation. This article gives a short overview of the mucosal barrier of the small intestine, summarizes the aspects of barrier dysfunction observed in all three gluten-related disorders and reviews literature data in favor of a primary involvement of the epithelial barrier in the development of celiac disease and non-celiac wheat sensitivity.
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Project description:Background and purposeAdiponectin, an adipokine possessing profound insulin-sensitizing and anti-inflammatory properties, is a potent biotherapeutic agent . The trimeric adiponectin subunit assembles into hexameric and functionally important higher molecular weight (HMW) forms, controlled by the endoplasmic reticulum protein 44 (ERp44). Obesity-induced ER stress decreases the HMW form in serum, contributing to the development of insulin resistance and Type 2 diabetes. In this study, a panel of synthetic peptides, designed to target ERp44-adiponectin interactions, were tested for their effects on circulating levels of HMW adiponectin.Experimental approachPeptides derived from the ERp44 binding region of adiponectin and immunoglobulin IgM were synthesized with or without a cell-penetrating sequence. Cultures of 3T3-L1 adipocytes were incubated with the peptides for assessing the assembly and secretion of HMW adiponectin. Mice given standard chow or a high-fat diet were treated acutely or chronically, with the peptides to investigate the therapeutic effects on insulin sensitivity and energy metabolism.ResultsThe designed peptides interfered with ERp44-adiponectin interactions and modulated adiponectin assembly and release from adipocytes. In particular, IgM-derived peptides facilitated the release of endogenous adiponectin (especially the HMW form) from adipose tissue, enhanced its circulating level and the ratio of HMW-to-total-adiponectin in obese mice. Long-term treatment of mice fed with high-fat diet by IgM-derived peptides reduced the circulating lipid levels and improved insulin sensitivity.Conclusions and implicationsTargeting ERp44-adiponectin interactions with short peptides represents an effective strategy to treat of obesity-related metabolic disorders, such as insulin resistance and Type 2 diabetes.
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Project description:Most common food grains contain gluten proteins and can cause adverse medical conditions generally known as gluten-related disorders. Celiac disease is an immune-mediated enteropathy triggered by gluten in individuals carrying a specific genetic make-up. The presence of the human leukocyte antigens (HLA)-DQ2 and HLA-DQ8 haplotypes together with gluten intake is a necessary, although not sufficient, condition, to develop celiac disease. Fine mapping of the human genome has revealed numerous genetic variants important in the development of this disease. Most of the genetic variants are small nucleotide polymorphisms located within promoters and transcriptional enhancer sequences. Their importance is underlined by an increased risk in DQ2/DQ8 carriers who also have these non-HLA alleles. In addition, several immune-mediated diseases share susceptibility loci with celiac disease, shedding light on the reasons for co-occurrence between these diseases. Finally, most of the genes potentially involved in celiac disease by fine genetic mapping of non-HLA loci were confirmed in gene expression studies. In contrast to celiac disease, very little is known about the genetic make-up of non-celiac wheat sensitivity (NCWS), a clinically defined pathology that shares symptoms and gluten dependence with the celiac disease. We recently identified differentially expressed genes and miRNAs in the intestinal mucosa of these patients. Remarkably, the differentially expressed genes were long non-coding RNAs possibly involved in the regulation of cell functions. Thus, we can speculate that important aspects of these diseases depend on alteration of regulatory genetic circuits. Furthermore, our finding suggests that innate immune response is involved in the pathogenic mechanism of NCWS. This review is intended to convey the idea that in order to fully understand celiac disease and its relationship with other gluten-related disorders, it is worth learning more about non-HLA variants.
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Project description:Gluten related disorders (GRD) represent a wide spectrum of clinical manifestations that are triggered by the ingestion of gluten. Coeliac disease (CD) or gluten sensitive enteropathy is the most widely recognised, but extra-intestinal manifestations have also been increasingly identified and reported. Such manifestations may exist in the absence of enteropathy. Gluten sensitivity (GS) is another term that has been used to include all GRD, including those where there is serological positivity for GS related antibodies in the absence of an enteropathy. Gluten ataxia (GA) is the commonest extraintestinal neurological manifestation and it has been the subject of many publications. Other movement disorders (MDs) have also been reported in the context of GS. The aim of this review was to assess the current available medical literature concerning MDs and GS with and without enteropathy. A systematic search was performed while using PubMed database. A total of 48 articles met the inclusion criteria and were included in the present review. This review highlights that the phenomenology of gluten related MDs is broader than GA and demonstrates that gluten-free diet (GFD) is beneficial in a great percentage of such cases.
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Project description:This cross-sectional study aims to assess eating competence (EC-an intra-individual approach to food, behaviors, and attitudes related to food) and aspects related to a gluten-free diet (GFD) in Brazilian adults with gluten-related disorders (GRDs). The research was conducted using an online survey with a self-reported instrument consisting of 40 items, organized into three parts: (I) Socioeconomic and demographic data; (II) the Brazilian version of the Eating Competence Satter Inventory (ec-SI2.0™BR); and (III) questions about adherence and difficulties in following the gluten-free diet. EC was measured by the ecSI2.0™BR instrument, with scores ≥32 were considered competent eaters. The instrument was applied nationwide through the GoogleForms® platform from 14 February 2022 to 30 March 2022. The publicity for the recruitment was supported by Brazilian celiac local and national associations (Acelbras and Fenacelbra), pages of food services or personal pages of tips and posts about gluten-related disorders, and specialized stores that offer gluten-free foods. The recruitment occurred through social networks (emails, Facebook groups, WhatsApp, and Instagram). A total of 1030 Brazilians with GRDs answered the questionnaire. Most participants were female, aged 40 years or older, with an income >R$3000, and a high education level. The main difficulty regarding adherence to GFD was the high cost of gluten-free foods. Individuals younger than 40 years old had lower EC scores, with no differences between men and women. Increasing socioeconomic status, schooling, and culinary practices increased the total score. Participants who "never/almost never" felt socially judged because their diet had higher scores for total EC. Competent eaters GRD individuals (EC ≥ 32) were mostly individuals aged ≥40 y/o; with income > R$3000; following a GFD; satisfied with purchased gluten-free products; consuming gluten-free products prepared at home, mainly by themselves; who do not feel judged because of the GRD and who feel that they can live a normal life with GRD. Our study showed that individuals who strictly adhere to the GFD have higher scores on eating competence than those who sometimes follow the treatment.
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Project description:The immunogenic potential of ?-gliadin protein from two ancient wheats was studied with reference to coeliac disease. To this aim we investigated Graziella Ra® and Kamut® (the latter is considered an ancient relative of modern durum wheat) in comparison to four durum wheat accessions (Senatore Cappelli, Flaminio, Grazia and Svevo). ELISA and Western Blot analyses - carried out by two monoclonal antibodies raised against the ?-gliadin peptides p31-49 (LGQQQPFPQQPYPQPQPF) and p56-75 (LQLQPFPQPQLPYPQPQLPY) containing a core region (underlined) reported to be toxic for coeliac patients - always showed an antibody-antigen positive reaction. For all accessions, an ?-gliadin gene has also been cloned and sequenced. Deduced amino acid sequences constantly showed the toxic motifs. In conclusion, we strongly recommend that coeliac patients should avoid consuming Graziella Ra® or Kamut®. In fact their ?-gliadin not only is as toxic as one of the other wheat accessions, but also occurs in greater amount, which is in line with the higher level of proteins in ancient wheats when compared to modern varieties.
| S-EPMC3257593 | biostudies-literature
Project description:Rothia mucilaginosa, a natural microbial inhabitant of the oral cavity, cleaves gluten (gliadin) proteins at regions that are resistant to degradation by mammalian enzymes. The aim of this study was to investigate to what extent the R. mucilaginosa cell-associated enzymes abolish gliadin immunogenic properties. Degradation of total gliadins and highly immunogenic gliadin 33-mer or 26-mer peptides was monitored by SDS-PAGE and RP-HPLC, and fragments were sequenced by liquid chromatography and electrospray ionization tandem mass spectrometer (LC-ESI-MS/MS). Peptide deamidation by tissue transglutaminase (TG2), a critical step in rendering the fragments more immunogenic, was assessed by TG2-mediated cross-linking to monodansyl cadaverine (MDC), and by a +1-Da mass difference by LC-ESI-MS. Survival of potential immunogenic gliadin epitopes was determined by use of the R5 antibody-based ELISA. R. mucilaginosa-associated enzymes cleaved gliadins, 33-mer and 26-mer peptides into smaller fragments. TG2-mediated cross-linking showed a perfect inverse relationship with intact 33-mer and 26-mer peptide levels, and major degradation fragments showed a slow rate of MDC cross-linking of 6.18 ± 2.20 AU/min compared with 97.75 ± 10.72 and 84.17 ± 3.25 AU/min for the intact 33-mer and 26-mer, respectively, which was confirmed by reduced TG2-mediated deamidation of the fragments in mass spectrometry. Incubation of gliadins with Rothia cells reduced R5 antibody binding by 20, 82, and 97% after 30 min, 2 h, and 5 h, respectively, which was paralleled by reduced reactivity of enzyme-treated 33-mer and 26-mer peptides in the R5 competitive ELISA. Our broad complementary approach to validate gluten degrading activities qualifies R. mucilaginosa-associated enzymes as promising tools to neutralize T cell immunogenic properties for treatment of celiac disease.
| S-EPMC4200315 | biostudies-literature