Coeliac disease: beyond genetic susceptibility and gluten. A narrative review

Coeliac disease (CD) is an immune-mediated disorder triggered by the ingestion of gluten in genetically susceptible individuals. However, only a small proportion of subjects harbouring CD-related genetic risk develop the disease. Among the environmental factors that may influence CD risk, pre- and perinatal factors, delivery methods, parental lifestyle, infant feeding practices, seasonality, dietary factors, drug use, childhood infections and variability in gut microbiota are those most widely studied regarding the risk to develop CD. Although for many of these external factors the exact mechanism of action is unknown, most of them are thought to act by disrupting the intestinal barrier, facilitating contact between potential antigens and the immune system effector cells. Management of CD is relatively easy in patients with a definite diagnosis and requires a strict, lifelong, gluten-free diet. Better knowledge of environmental exposures apart from gluten can facilitate understanding of the pathogenesis of the disorder and the wide heterogeneity of its clinical spectrum. The purpose of this review is to discuss current knowledge on environmental CD risk factors, as well as possible interaction between them, on the grounds of the reliable scientific evidence available. Key messages The risk of developing CD is influenced not only by gluten ingestion but also by a number of environmental factors including childhood infections and variability in gut microbiota, pre- and perinatal factors, infant feeding practices, delivery methods, parental lifestyle, seasonality, dietary factors and drug use, acting mainly by disrupting intestinal permeability. Better knowledge of exposure to these factors can facilitate their identification, and subsequent elimination, in the individual patient.