Todd Katlyn, Gunter Krista, Bowen James M, Holmes Caitlyn L, Tilston-Lunel Natasha L, Vornhagen Jay
Department of Microbiology & Immunology, Indiana University School of Medicine, Indiana University, Indianapolis, USA.
Department of Pathology, Michigan Medicine, University of Michigan, Ann Arbor, MI, USA.
bioRxiv. 2024 May 31:2024.05.31.596766. doi: 10.1101/2024.05.31.596766.
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.
是一种机会致病菌，是肺炎、菌血症和尿路感染的重要病因。感染在历史上与糖尿病相关。我们对糖尿病，特别是2型糖尿病如何影响其发病机制的理解存在根本差距。其发病机制是一个多因素过程，通常始于肠道定植，随后从肠道逃逸到外周部位，导致宿主损伤和感染。我们假设2型糖尿病会增强其发病机制。为了验证这一点，我们将成熟的定植和肺部感染小鼠模型与自发性2型糖尿病（T2DM）小鼠模型结合使用。我们发现T2DM会增加对定植和感染的易感性。肠道定植的增强取决于T2DM诱导的肠道微生物群落结构的调节。相比之下，肺部感染因肺部氨基酸可用性增加而加剧，这与血管内皮生长因子水平升高有关。这些数据为深入研究其发病机制与2型糖尿病之间的关系奠定了基础，并明确将T2DM确定为该疾病的一个危险因素。
