Gut microbiota and type 1 diabetes

Outi Vaarala

Immune Response Unit, Department of Vaccination and Immune Protection, National Institute for Health and Welfare, Helsinki, Finland

Abstract

The gut immune system has a key role in the development of autoimmune diabetes, and thus the factors, which regulate the gut immune system are also regulators of beta-cell autoimmunity. Gut microbiota modulate the function of the gut immune system by its effects on the innate immune system, such as the intestinal epithelial cells and dendritic cells, and on the adaptive immune system, in particular intestinal T cells. Due to the immunological link between gut and pancreas, e.g. the shared lymphocyte homing receptors, the immunological changes in the gut are reflected in the pancreas. According to animal studies, changes in the gut microbiota alter the development of autoimmune diabetes. This has been demonstrated by antibiotics, inducing changes in the gut microbiota. Also, gut-colonising microbes may modify the incidence of autoimmune diabetes in animal models. Deficient TLR signalling mediating microbial stimulus in the immune cells prevent autoimmune diabetes, which appears to be dependent on alterations in the intestinal microbiota. Although studies in humans are limited in number, recent studies suggest that the abundance of Bacteroides and low numbers of butyrate-producing bacteria in fecal microbiota are associated with beta-cell autoimmunity and type 1 diabetes. Altered gut microbiota could be associated with immunological aberrancies in type 1 diabetes. The changes in gut microbiota could lead to alterations in the gut immune system, such as increased gut permeability, small intestinal inflammation, and impaired tolerance to food antigens, all of which are observed in type 1 diabetes. Poor fitness of gut microbiota could explain why children who develop type 1 diabetes are prone to enterovirus infections, and do not develop tolerance to cow milk antigens. These candidate risk factors of type 1 diabetes may imply an increased risk of type 1 diabetes due to the presence of gut microbiota not supporting health. Despite the complex interaction of microbiota, host, environment, and disease mechanisms, interventions targeting gut microbiota are promising avenues to prevent type 1 diabetes.