Published online Nov 14, 2017. doi: 10.3748/wjg.v23.i42.7505
Peer-review started: May 23, 2017
First decision: June 23, 2017
Revised: July 31, 2017
Accepted: August 15, 2017
Article in press: August 15, 2017
Published online: November 14, 2017
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.
Core tip: There is evidence that the host-microbiota homeostasis is disrupted in celiac disease (CD) patients. Dysbiosis, meaning an imbalance in the gut microbiota and its metabolome, may activate innate immunity leading to pro-inflammatory changes, which induces intraepithelial lymphocyte infiltration and epithelial barrier damage, ultimately resulting in increased transfer of gluten peptides and inflammatory activation leading to CD development. The intestinal microbiota also has a direct effect on the breakdown of gluten and formation of immunogenic peptides. As colonization of the gut with microorganisms may be dependent on genetic factors, future prophylactic strategies may focus on gut microbiota modulation in genetically predisposed infants.