The Role of Gut Microbiota on Cholesterol Metabolism in Atherosclerosis

Abstract

Hypercholesterolemia plays a causal role in the development of atherosclerosis and is one of the main risk factors for cardiovascular disease (CVD), the leading cause of death worldwide especially in developed countries. Current data show that the role of microbiota extends beyond digestion by being implicated in several metabolic and inflammatory processes linked to several diseases including CVD. Studies have reported associations between bacterial metabolites and hypercholesterolemia. However, such associations remain poorly investigated and characterized. In this review, the mechanisms of microbial derived metabolites such as primary and secondary bile acids (BAs), trimethylamine N-oxide (TMAO), and short-chain fatty acids (SCFAs) will be explored in the context of cholesterol metabolism. These metabolites play critical roles in maintaining cardiovascular health and if dysregulated can potentially contribute to CVD. They can be modulated via nutritional and pharmacological interventions such as statins, prebiotics, and probiotics. However, the mechanisms behind these interactions also remain unclear, and mechanistic insights into their impact will be provided. Therefore, the objectives of this paper are to present current knowledge on potential mechanisms whereby microbial metabolites regulate cholesterol homeostasis and to discuss the feasibility of modulating intestinal microbes and metabolites as a novel therapeutic for hypercholesterolemia.

Comparison between Egg Intake versus Choline Supplementation on Gut Microbiota and Plasma Carotenoids in Subjects with Metabolic Syndrome

“…Except for the correlation between bacterial diversity and HDL cholesterol, the other parameters directly related to MetS (such as BMI, SBP, DBP, WC, triglyceride, glucose, and insulin) were not significantly different between the treatments. This correlation indicates the association of gut microbiota with lipid metabolism [ 69 ].…”

Pathophysiological Potentials of NRF3-Regulated Transcriptional Axes in Protein and Lipid Homeostasis

“…Dietary cholesterol in the blood is absorbed in the intestine [ 61 ], and its dysregulation is associated with obesity, resulting in an increased risk of cardiovascular diseases (CVD) and colorectal cancer [ 62 , 63 ]. The gut microbiota has been identified as a CVD risk factor and regulates host cholesterol homeostasis [ 64 , 65 , 66 ], suggesting the pathophysiological potential of the NRF3-regulated host lipid metabolism to the gut–heart connection through the gut microbiota.…”

Lymphatic Vessel Regression and Its Therapeutic Applications: Learning From Principles of Blood Vessel Regression

“…Lymphatic vessel regression has been hypothesized to exacerbate atherosclerotic cardiovascular disease, the leading cause of death worldwide ( Csányi and Singla, 2019 ; Vourakis et al, 2021 ). In health, the lymphatic system serves as a conduit for reverse cholesterol transport, the process by which peripheral cholesterol is retrieved and shuttled to the liver by high-density lipoproteins (HDLs) ( Huang et al, 2015 ).…”