The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

Abstract

The gut microbiota has emerged as a contributing factor in the development of atherosclerosis and arterial thrombosis. Metabolites from the gut microbiota, such as trimethylamine N-oxide and short chain fatty acids, were identified as messengers that induce cell type-specific signaling mechanisms and immune reactions in the host vasculature, impacting the development of cardiovascular diseases. In addition, microbial-associated molecular patterns drive atherogenesis and the microbiota was recently demonstrated to promote arterial thrombosis through Toll-like receptor signaling. Furthermore, by the use of germ-free mouse models, the presence of a gut microbiota was shown to influence the synthesis of endothelial adhesion molecules. Hence, the gut microbiota is increasingly being recognized as an influencing factor of arterial thrombosis and attempts of dietary pre- or probiotic modulation of the commensal microbiota, to reduce cardiovascular risk, are becoming increasingly significant.

Keywords: arterial thrombosis; blood pressure regulation; cardiovascular disease; gut microbiota; vascular inflammation.

Figure 1

Atherosclerosis in antibiotic-treated mice and in the germ-free Apoe-deficient mouse model. (A) Pro-atherogenic effects are described for the choline-rich diet and the microbiota-derived choline-metabolite trimethylamine N-oxide (TMAO) [12,13,16]. (B) GF Apoe-deficient mice on a chow-diet developed an increased lesion size compared to CONV-R Apoe-deficient mice and the gut microbiota had a cholesterol-lowering function under chow-diet conditions [9,10,14,15].

Figure 2

Evidence for a pro-thrombotic role of the gut microbiota as identified by gnotobiotic mouse models. Serotonin from enterochromaffin cells in the intestinal epithelial lining and the microbiota-derived choline-metabolite trimethylamine N-oxide (TMAO) were described to promote platelet reactivity, following agonist-induced platelet activation [82,88]. The gut microbiota increases the expression of endothelial adhesion molecules, such as ICAM-1 and VWF [95,96].