Type-2 diabetes mellitus enhances pathogenesis.

is an opportunistic pathogen and an important cause of pneumonia, bacteremia, and urinary tract infection. infections are historically associated with diabetes mellitus. There is a fundamental gap in our understanding of how diabetes mellitus, specifically type 2 diabetes, influences pathogenesis. pathogenesis is a multifactorial process that often begins with gut colonization, followed by an escape from the gut to peripheral sites, leading to host damage and infection. We hypothesized that type 2 diabetes enhances pathogenesis. To test this, we used well-established mouse models of colonization and lung infection in conjunction with a mouse model of spontaneous type 2 diabetes mellitus (T2DM). We show that T2DM enhances susceptibility to both colonization and infection. The enhancement of gut colonization is dependent on T2DM-induced modulation of the gut microbiota community structure. In contrast, lung infection is exacerbated by the increased availability of amino acids in the lung, which is associated with higher levels of vascular endothelial growth factor. These data lay the foundation for mechanistic interrogation of the relationship between pathogenesis and type 2 diabetes mellitus, and explicitly establish T2DM as a risk factor for disease.