Modulation of Type 1 and Type 2 Diabetes Risk by the Intestinal Microbiome

The prevalence of type 1 and type 2 diabetes have both risen dramatically over the last 50 years. Recent findings point towards the gut microbiota as a potential contributor to these trends. The hundred trillion bacteria residing in the mammalian gut have established a symbiotic relation with their host and influence many aspects of host metabolism, physiology, and immunity. In this review, we examine recent data linking gut microbiome composition and function to anti-pancreatic immunity, insulin-resistance, and obesity. Studies in rodents and human longitudinal studies suggest that an altered gut microbiome characterized by lower diversity and resilience is associated with type 1 and type 2 diabetes. Through its metabolites and enzymatic arsenal, the microbiota shape host metabolism, energy extracted from the diet and contribute to the normal development of the immune system and to tissue inflammation. Increasing evidence underscores the importance of the maternal microbiome, the gestational environment and the conditions of newborn delivery in establishing the gut microbiota of the offspring. Perturbations of the maternal microbiome during gestation, or that of the offspring during early infant development may promote a pro-inflammatory environment conducive to the development of autoimmunity and metabolic disturbance. Collectively the findings reviewed herein underscore the need for mechanistic investigations in rodent models and in human studies to better define the relationships between microbial and host inflammatory activity in diabetes, and to evaluate the potential of microbe-derived therapeutics in the prevention and treatment of both forms of diabetes.