The gut microbiota: An emerging risk factor for cardiovascular and cerebrovascular disease.

Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury. Depending on nutritional factors, the microbiota-derived choline-metabolite trimethylamine N-oxide (TMAO) increases atherosclerotic plaque size, triggers prothrombotic platelet function and promotes arterial thrombus growth. Hence, the composition of the commensal microbiota is an emerging risk factor for CVD. Here, we provide an overview on microbiota-dependent pathomechanisms that drive the development of CVD and arterial thrombosis.