Intestinal Barrier Function in Gluten-Related Disorders

Nutrients. 2019 Oct 1;11(10):2325. doi: 10.3390/nu11102325.


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.

Keywords: celiac disease; epithelial barrier; non-celiac gluten sensitivity; non-celiac wheat sensitivity; permeability; wheat allergy.

Publication types

  • Review

MeSH terms

  • Animals
  • Bacteria / immunology
  • Bacteria / metabolism
  • Celiac Disease / drug therapy
  • Celiac Disease / immunology
  • Celiac Disease / metabolism*
  • Celiac Disease / microbiology
  • Gastrointestinal Agents / therapeutic use
  • Gastrointestinal Microbiome
  • Glutens / immunology
  • Glutens / metabolism*
  • Host-Pathogen Interactions
  • Humans
  • Immunity, Innate
  • Intestinal Absorption* / drug effects
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism*
  • Intestinal Mucosa / microbiology
  • Intestine, Small / drug effects
  • Intestine, Small / immunology
  • Intestine, Small / metabolism*
  • Intestine, Small / microbiology
  • Oligopeptides / therapeutic use
  • Permeability
  • Signal Transduction
  • Tight Junction Proteins / metabolism
  • Wheat Hypersensitivity / drug therapy
  • Wheat Hypersensitivity / immunology
  • Wheat Hypersensitivity / metabolism*
  • Wheat Hypersensitivity / microbiology


  • Gastrointestinal Agents
  • Oligopeptides
  • Tight Junction Proteins
  • Glutens
  • larazotide acetate