The gut microbiota is an environmental factor that impacts vascular physiology, locally in the intestine, but also through remote signaling. Dependent on diet, numerous mouse studies demonstrated that this gut-resident microbial ecosystem affects atherogenesis. Atherosclerotic lesion formation can be influenced by gut microbial metabolites, but also by microbiota-derived microbial-associated molecular patterns that reach the circulation and affect endothelial cell activation and organ-specific immunity. Dr. Reinhardt and others showed reduced thrombus growth in germ-free mice in various carotid artery injury models, implicating gut microbiota in arterial thrombosis. The deposition of platelets at the site of vascular injury in germ-free mice was diminished due to reduced von Willebrand factor plasma levels and impaired platelet integrin function. This recent evidence broadens our perception of colonizing gut microbes beyond their established role in blood-stream infections.