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.
Highlights
The family of claudins play a crucial role in tight junctions (TJ) formation and the epithelial barrier, but they have functions in cytoskeleton organization, transport of vesicles and signaling pathways directly associated with scaffold proteins such as ZO-1 [32]
In active and refractory celiac disease (CeD) (RCD, a small CeD subgroup not responding to at least one year of gluten-free diet (GFD)), intraepithelial lymphocytes (IELs) are activated by the upregulation of IL-15, which leads to epithelial cell destruction and subsequently barrier dysfunction [61,62,63]
CeD is regarded as a T-cell disease involving gliadin-specific T-cells, recent research has revealed a role for barrier function in the induction phase of the disease
Summary
The intestinal barrier has a crucial role in protecting the organism against pathogens and possible harmful substances derived from the external environment (Figure 1). It is formed by a mucus and epithelial layer and by the lamina propria underneath. Components of the intestinal microbiota and anti-microbial peptides have crucial functions in maintaining the intestinal barrier function [1,2]
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