1. Figure 2 Microbiota-related pathways in atherosclerosis
Figure 2 | Microbiota-related pathways in atherosclerosis. Microbiota can affect atherosclerosis by three different pathways. First, bacterial infection activates the immune system causing a harmful inflammatory response. Both local infections by bacteria invading the atherosclerotic plaque and distant infection can lead to a proatherogenic response. Infections lead to an increase in proinflammatory cytokines and chemokines, which could be mediated by Toll-like receptor 4 expressed in macrophages. The proinflammatory response, regardless of bacterial infection site (vessel wall or distant site), might affect the progression of atherosclerosis and potentially also vulnerability of the plaque. Second, microbiota can influence atherosclerosis through altered cholesterol metabolism. The microbiota alters the levels of serum triglycerides and cholesterol, and bacterial taxa in the oral cavity and gut correlate with serum cholesterol6. Gut bacteria are also important in modifying bile acids, which function as signalling molecules through the farnesoid X receptor (FXR). Activation of FXR induces flavin monooxygenase 3 (FMO3) in the liver; this enzyme converts trimethylamine (TMA) to trimethylamine N-oxide (TMAO). Third, specific dietary components and microbial metabolites can lead to the production of both beneficial and harmful molecules. These pathways might contribute to the development of atherosclerotic plaques and might also augment the disease, causing plaque rupture and thrombosis. Increased serum levels of TMAO, a bacterial-derived metabolite from choline and carnitine, are associated with CVD. Some effects of TMAO are directly related to atherogenesis, such as the inhibition of reverse cholesterol transport (RCT) and the increase in foam cell formation, and indirect metabolic effects such as the inhibition of enzymes involved in bile acid synthesis (cholesterol 7α-monooxygenase [Cyp7a1] and sterol 26-hydroxylase, mitochondrial [Cyp27a1])85 might also affect plaque development. The effects of dietary fibre and the bacteria-induced formation of short-chain fatty acids such as acetate, butyrate, and propionate are not clear, but might involve an overall reduction in systemic inflammation. LPS, lipopolysaccharide.
Jonsson, A. L. & Bäckhed, F. (2016) Role of gut microbiota in atherosclerosis
Nat. Rev. Cardiol. doi: /nrcardio