Gut microbiota and cardiovascular disease: opportunities and challenges

Abstract

Coronary artery disease (CAD) is the most common health problem worldwide and remains the leading cause of morbidity and mortality. Over the past decade, it has become clear that the inhabitants of our gut, the gut microbiota, play a vital role in human metabolism, immunity, and reactions to diseases, including CAD. Although correlations have been shown between CAD and the gut microbiota, demonstration of potential causal relationships is much more complex and challenging. In this review, we will discuss the potential direct and indirect causal roots between gut microbiota and CAD development via microbial metabolites and interaction with the immune system. Uncovering the causal relationship of gut microbiota and CAD development can lead to novel microbiome-based preventative and therapeutic interventions. However, an interdisciplinary approach is required to shed light on gut bacterial-mediated mechanisms (e.g., using advanced nanomedicine technologies and incorporation of demographic factors such as age, sex, and ethnicity) to enable efficacious and high-precision preventative and therapeutic strategies for CAD.

Fig. 1

Cholesterol, gut microbiota, and CAD. a Exogenous and endogenous sources of luminal cholesterol. b The multifaceted mechanisms involved in CAD development. The gut microbiota can directly (via metabolites) and indirectly (via the immune system) lead to CAD

Fig. 2

Multifaceted mechanisms affecting CAD. Exogenous and endogenous sources of luminal cholesterol and diet, and the gut microbiota mechanisms involved in affecting the immune system and CAD development

Fig. 3

Microbiota, diet, and CAD. Diet directly and indirectly affects cholesterol levels and CAD development via the consumption of cholesterol-rich foods, can affect on the immune system, and lead to the modulation of gut microbiota and their metabolites such as bile acids, coprostanol, SCFA, and TMAO

Fig. 4

Microbiota, aging, and CAD. Selected aging-related mechanisms involved in systemic inflammation and adverse health outcomes. SCFA short chain fatty acid, WBC white blood cells, HDL high-density lipoprotein, LDLR low-density lipoprotein receptor, CYP7A1 cholesterol 7-alpha-hydroxylase1, LDL low-density lipoprotein, NPC1L1 Niemann-Pick C1-like1, ROS reactive oxygen species

Fig. 5

Nanomedicine, microbiota, and CAD. Nanoparticles in nanomedicine have many applications that can aid in the prevention, diagnosis, and treatment of CAD. The utilization of nanoparticles to understand the underlying bodily mechanisms (i.e., protein corona analysis), drug delivery (i.e., microbiome- and metabolome-targeted therapies), and scavenging particles (i.e., for LDL cholesterol modulating the immune system) can lead to a healthier gut microbiome and immune system that result in better overall healthy state clear of CAD development