Role of viruses and other microbes in the pathogenesis of type 1 diabetes.

Type 1 diabetes is caused by an immune-mediated destruction of insulin producing beta-cells in the pancreas. The risk of the disease is determined by interactions between more than 40 different susceptibility genes and yet unidentified environmental factors. The rapidly increasing incidence indicates that these environmental agents have a significant role in the pathogenesis. Microbes have associated with both increased and decreased risk reflecting their possible role as risk or protective factors. Two main hypotheses have been proposed to explain these effects: the hygiene hypothesis suggests that microbial exposures in early childhood stimulate immunoregulatory mechanisms which control autoimmune reactions (analogy with allergy), while the triggering hypothesis suggests that specific microbes damage insulin producing cells. Certain viruses, particularly enteroviruses, are currently the main candidates for such risk microbes. Enteroviruses cause diabetes in animals and have associated with increased risk of type 1 diabetes in epidemiological studies. They have also been detected in the pancreas of diabetic patients. Possible protective effect of microbes has been studied in animal models and in epidemiological studies, where certain enteral microbes (e.g. hepatitis A virus and Helicobacter pylori) and patterns of gut microbiome have associated with low risk of type 1 diabetes. In conclusion, these microbial effects offer attractive possibilities for the development of preventive interventions for type 1 diabetes based on the elimination of triggering agents (e.g. enterovirus vaccines) or use of protective microbes as probiotics.