The gut microbiota and its interactions with cardiovascular disease

Abstract

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis. Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD). Moreover, the effects of imbalances in microbe-host interactions on homeostasis can lead to the progression of CVD. Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD. Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N-oxide, short-chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways. Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment. The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors. Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

Figure 1

Schematic illustration of the links between the gut microbiota, TMAO and CVD. Dietary trimethylammonium (e.g. phosphatidylcholine, choline and l‐carnitine) can be metabolized into trimethylamine (TMA) by the gut microbiota. In the liver, TMA is converted into trimethylamine N‐oxide (TMAO) by flavin‐containing monooxygenases (FMOs). The effects of TMAO are associated with foam cell formation, alterations in cholesterol metabolism, platelet hyper‐responsiveness, vascular inflammation and adverse cardiac remodelling, all of which can contribute to CVD.

Figure 2

Diagram of the cardiovascular risks associated with inflammation, lipid metabolism disorders and diabetes related to gut microbial ecology. The gut microbiota interacts with the host immune system to maintain gut–barrier functions. Pathological disorders, including ischaemia and oedema, are associated with alterations in gut–barrier functions. A leaky intestinal barrier allows for increased flux of pro‐inflammatory bacterial products into the circulation, causing chronic low‐grade inflammation mainly via TLR activation. Consequently, elevated levels of inflammatory cytokines in the bloodstream are potent inducers of intestinal permeability, thus resulting in the formation of a vicious cycle that promotes toxic molecule translocation and inflammation. Furthermore, TLR activation also contributes to insulin resistance. Changes in the gut microbial composition are related to abnormal serum lipid levels and other adverse metabolic effects, whereas some species shifts result in beneficial effects on metabolism. As for gut microbial metabolites, TMAO induces diabetes‐related metabolic effects and disrupts cholesterol metabolism, whereas urolithin A, urolithin B, NAPEs and SCFAs have protective properties. Molecules such as DPP‐4, SGLT2, GLP‐1 and MyD88 are potential mediators that link the gut microbiota to CVD risk. Diabetes and lipid metabolism disorders, together with inflammation, are risk factors that contribute to CVD development and progression. The brown arrows with single arrowhead indicate the effects of promotion, whereas the horizontal T shape indicates the effects of inhibition; the brown arrows with double arrowhead indicate the interactions with each other; the brown arrow in dash line indicates the feedback; the black arrows indicate the elevation and reduction.

Figure 3

Interventions that target the gut microbiota for improving CVD therapeutics. Increasing evidence has proven the link between the gut microbiota and CVD, indicating that modification of the intestinal microbiota could help to prevent and manage CVD. Current strategies for manipulating gut microbes to elicit positive effects on the cardiovascular system include dietary interventions, use of pre‐ or probiotics and antibiotics, faecal microbiota transplantation, TMAO reduction and exercise.