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Intestinal Barrier Function in Gluten-Related Disorders.

ABSTRACT: 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.

SUBMITTER: Cardoso-Silva D

PROVIDER: S-EPMC6835310 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Intestinal Barrier Function in Gluten-Related Disorders.

Cardoso-Silva Danielle D Delbue Deborah D Itzlinger Alice A Moerkens Renée R Withoff Sebo S Branchi Federica F Schumann Michael M

Nutrients 20191001 10

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 aller ...[more]

PMID: 31581491

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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.

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.

Dataset Information

Intestinal Barrier Function in Gluten-Related Disorders.

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Intestinal Barrier Function in Gluten-Related Disorders.

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