Based all above, we intended to clarify the specific role of the GM and its metabolites in the pathogenesis of diabetes and associated chronic complications, particularly how they influence insulin sensitivity and glucose homeostasis in the host through impacting metabolic pathways and inflammatory responses, and these results may pioneer new avenues for the prevention and treatment of hyperglycemia, especially slow down or potentially reverse the progression of diabetes by modulating the composition and function of the GM and/or supplementing the metabolites derived from the GM. Here, INS is linked to diabetes mellitus.