Bridging the Gap between Gut Microbial Dysbiosis and Cardiovascular Diseases

Abstract

The human gut is heavily colonized by a community of microbiota, primarily bacteria, that exists in a symbiotic relationship with the host and plays a critical role in maintaining host homeostasis. The consumption of a high-fat (HF) diet has been shown to induce gut dysbiosis and reduce intestinal integrity. Recent studies have revealed that dysbiosis contributes to the progression of cardiovascular diseases (CVDs) by promoting two major CVD risk factors—atherosclerosis and hypertension. Imbalances in host–microbial interaction impair homeostatic mechanisms that regulate health and can activate multiple pathways leading to CVD risk factor progression. Dysbiosis has been implicated in the development of atherosclerosis through metabolism-independent and metabolite-dependent pathways. This review will illustrate how these pathways contribute to the various stages of atherosclerotic plaque progression. In addition, dysbiosis can promote hypertension through vascular fibrosis and an alteration of vascular tone. As CVD is the number one cause of death globally, investigating the gut microbiota as a locus of intervention presents a novel and clinically relevant avenue for future research, with vast therapeutic potential.

The Potential of Probiotics in the Prevention and Treatment of Atherosclerosis

“…In this study, icosapent ethyl, a highly purified ethyl ester of eicosapentaenoic acid omega‐3 PUFA, was found to significantly reduce the risk of major adverse cardiovascular events by 25% . In addition to these nutraceuticals, recent studies have revealed an association between atherosclerosis‐associated CVD and gut microbial dysbiosis, and probiotic bacteria have been highlighted as potential candidates for atherosclerosis intervention.…”

“…The intestinal barrier is an epithelial monolayer that forms a primary interface preventing the diffusion of potentially injurious factors from the intestinal lumen into the tissue and systemic circulation . Dysbiosis in the gut compromises the intestinal barrier function leading to the leakage of lipopolysaccharide (LPS) and other bacterial components (e.g., peptidoglycans) into the circulation, triggering an inflammatory response that drives atherosclerosis . LPS is able to promote monocyte recruitment to the activated endothelium and subsequent macrophage foam cell formation by stimulating the uptake of modified LDL and reducing the efflux of cholesterol from foam cells .…”

“…Dysbiosis in the gut compromises the intestinal barrier function leading to the leakage of lipopolysaccharide (LPS) and other bacterial components (e.g., peptidoglycans) into the circulation, triggering an inflammatory response that drives atherosclerosis . LPS is able to promote monocyte recruitment to the activated endothelium and subsequent macrophage foam cell formation by stimulating the uptake of modified LDL and reducing the efflux of cholesterol from foam cells . LPS is also able to induce vascular inflammation either directly or via the production of pro‐inflammatory factors from immune cells .…”

“…LPS is also able to induce vascular inflammation either directly or via the production of pro‐inflammatory factors from immune cells . Toll‐like receptors (TLRs) are a family of recognition receptors for pathogen associated molecular patterns (PAMPs), activated in response to bacterial components such as LPS . Upon activation of TLRs, an inflammatory response is orchestrated via intracellular signaling cascades that induces the expression of many pro‐inflammatory cytokines and chemokines .…”

“…Toll‐like receptors (TLRs) are a family of recognition receptors for pathogen associated molecular patterns (PAMPs), activated in response to bacterial components such as LPS . Upon activation of TLRs, an inflammatory response is orchestrated via intracellular signaling cascades that induces the expression of many pro‐inflammatory cytokines and chemokines . Furthermore, microbiota‐derived metabolites, including atherogenic molecules such as choline and trimethylamine N ‐oxide (TMAO) link the gut microbiome to disease (see Section 10).…”