Intestinal epithelium, intraepithelial lymphocytes and the gut microbiota - Key players in the pathogenesis of celiac disease

Abstract

Celiac disease (CD) is a chronic immune-mediated disorder triggered by the ingestion of gluten in genetically predisposed individuals. Before activating the immune system, gluten peptides are transferred by the epithelial barrier to the mucosal lamina propria, where they are deamidated by intestinal tissue transglutaminase 2. As a result, they strongly bind to human leucocyte antigens (HLAs), especially HLA-DQ2 and HLA-DQ8, expressed on antigen-presenting cells. This induces an inflammatory response, which results in small bowel enteropathy. Although gluten is the main external trigger activating both innate and adaptive (specific) immunity, its presence in the intestinal lumen does not fully explain CD pathogenesis. It has been hypothesized that an early disruption of the gut barrier in genetically susceptible individuals, which would result in an increased intestinal permeability, could precede the onset of gluten-induced immune events. The intestinal barrier is a complex functional structure, whose functioning is dependent on intestinal microbiota homeostasis, epithelial layer integrity, and the gut-associated lymphoid tissue with its intraepithelial lymphocytes (IELs). The aim of this paper was to review the current literature and summarize the role of the gut microbiota, epithelial cells and their intercellular junctions, and IELs in CD development.

Prevalence and characteristics of celiac disease in South African patients with type 1 diabetes mellitus: Results from the Durban Diabetes and Celiac Disease Study

“…39 Increased intestinal permeability via exposure to gliadin or certain gut microbiota has been linked to the pathogenesis of CD and may account for the rates of AGA positivity in this study and warrants further investigation. 40 The use of immunoassays alone for diagnosis has been recommended for resource-poor settings where duodenal biopsy is not available. 9 However, the low positive predictive value of celiac antibodies in this study highlights the short-coming of this strategy.…”

Intestinal barrier integrity in patients with plaque psoriasis

“…Alteration in the gut microbiome may affect intestinal integrity and increase gut permeability leading to local and systemic immune response . Intestinal barrier disruption, along with genetic background and environmental factors, has been recently considered as a pivotal element in the pathogenesis of chronic inflammatory diseases, including inflammatory bowel disease and celiac disease . Recent experimental and clinical studies revealed disturbance in the balance of beneficial and pathogenic bacteria in the gut of patients with psoriasis and psoriatic arthritis .…”

“…3 Intestinal barrier disruption, along with genetic background and environmental factors, has been recently considered as a pivotal element in the pathogenesis of chronic inflammatory diseases, including inflammatory bowel disease and celiac disease. 4,5 Recent experimental and clinical studies revealed disturbance in the balance of beneficial and pathogenic bacteria in the gut of patients with psoriasis and psoriatic arthritis. [6][7][8] However, it remains unclear whether alteration in the gut microbiome and inflammatory processes in psoriasis influence the intestinal barrier.…”

Human leukocyte antigen DQ2/DQ8 positivity in women with history of stillbirth

“…27 Inflammation, subsequent to an impaired intestinal barrier, composition. 29,30 We speculated that the maternal inflammation caused by alteration of intestinal flora could mislead changes in nutrient supply, oxygen, and alterations in the secretion of hormones and other signaling molecules in the fetal circulation. 28 An imbalance in the gut microbiota may produce lactate or butyrate, which could regulate gut permeability and induce the gut inflammatory, lipopolysaccaharides infiltration, oxidative stress, macrophage infiltration, and consequently chronic low grade inflammation.…”