The role of gut dysbiosis and mitochondrial dysfunction in type 2 diabetes: Insights on pathogenesis, intervention and future perspective

Type 2 diabetes (T2D) is a typical metabolic disease which is attributed to genetic and environmental factors. Emerging evidence has highlighted that either gut dysbiosis or mitochondrial dysfunction plays critical roles in the development of T2D through various ways. After searching preclinical and clinical studies, our review concludes that gut dysbiosis contribute to T2D through gut metabolites-induced inflammation, dysregulation of glucose homeostasis and the change of β-cell evolution. Moreover, we found out that the overproduction of oxidative stress, disruption of energy metabolism, mitochondrial dynamic network and mitochondrial permeability transition are major mechanisms which contribute to the development of T2D by mitochondrial dysfunction. We particularly focused on summarizing the advances of how gut dysbiosis and mitochondrial dysfunction contributed to T2D development, respectively, and elaborating their interplay in central and peripheral organs. Moreover, the latest strategies on T2D management were also discussed, in which modulation on gut microbiota and mitochondrial function were primarily included, as well as perspectives on future investigations.