Type 2 Diabetes and the Microbiome.

Diabetes represents one of the most significant, and rapidly escalating, global healthcare crises we face today. Diabetes already affects one-tenth of the world's adults-more than 537 million people, numbers that have tripled since 2000 and are estimated to reach 643 million by 2030. Type 2 diabetes (T2D), the most prevalent form, is a complex disease with numerous contributing factors, including genetics, epigenetics, diet, lifestyle, medication use, and socioeconomic factors. In addition, the gut microbiome has emerged as a significant potential contributing factor in T2D development and progression. Gut microbes and their metabolites strongly influence host metabolism and immune function, and are now known to contribute to vitamin biosynthesis, gut hormone production, satiety, maintenance of gut barrier integrity, and protection against pathogens, as well as digestion and nutrient absorption. In turn, gut microbes are influenced by diet and lifestyle factors such as alcohol and medication use, including antibiotic use and the consumption of probiotics and prebiotics. Here we review current evidence regarding changes in microbial populations in T2D and the mechanisms by which gut microbes influence glucose metabolism and insulin resistance, including inflammation, gut permeability, and bile acid production. We also explore the interrelationships between gut microbes and different T2D medications and other interventions, including prebiotics, probiotics, and bariatric surgery. Lastly, we explore the particular role of the small bowel in digestion and metabolism and the importance of studying small bowel microbes directly in our search to find metabolically relevant biomarkers and therapeutic targets for T2D.