Exploring the Gut-Heart Axis: How Gut Microbiome Composition Influences Coronary Artery Disease Development and Progression

Robert Pogue^*
*Correspondence: Robert Pogue, Department of Cardiology, University of Oulu, Pentti Kaiteran katu 1, 90570 Oulu, Finland, Email:

Introduction

Coronary artery disease is a leading cause of morbidity and mortality worldwide. While traditional risk factors such as diet, exercise, and genetics play a significant role in its development, emerging research has unveiled the intricate relationship between the gut microbiome and CAD. The gut-heart axis represents a bidirectional communication system whereby the gut microbiome influences cardiovascular health and vice versa. This review explores the current understanding of how gut microbiome composition contributes to CAD pathogenesis and progression, highlighting the potential for microbiome-based interventions as a novel approach for CAD prevention and management.

Coronary artery disease is characterized by the accumulation of atherosclerotic plaques within coronary arteries, leading to reduced blood flow and potentially fatal myocardial infarction. Traditional risk factors include hypertension, hyperlipidemia, smoking, diabetes, and family history. However, recent advancements in microbiome research have uncovered a new dimension to CAD pathogenesis, implicating the gut microbiome in influencing cardiovascular health. The gut-heart axis, a bidirectional communication system between the gut microbiome and cardiovascular system, has gained attention for its potential role in CAD development and progression. The human gut harbors a diverse community of microorganisms, collectively termed the gut microbiome. Its composition is influenced by various factors, including diet, genetics, age, and medication use. Dysbiosis, an imbalance in the gut microbiome composition, has been linked to several chronic diseases, including CAD. Studies have demonstrated alterations in gut microbial diversity and abundance in CAD patients, suggesting a potential role in disease pathogenesis [1-3].

Description

Gut microbiome metabolism and CAD

The human gut microbiome plays a crucial role in metabolizing dietary compounds, producing a wide array of metabolites that can impact both local and systemic physiological processes. Emerging evidence suggests that certain microbial metabolites generated within the gut have a significant influence on the development and progression of coronary artery disease. One of the most extensively studied gut microbiome-related metabolites in the context of CAD is trimethylamine N-oxide. TMAO is produced in a multi-step process involving the gut microbiota, liver, and kidney. It is derived from dietary sources rich in choline, phosphatidylcholine, and carnitine, which are abundant in red meat, eggs, and dairy products. The gut microbiota convert these precursors into trimethylamine, which is then absorbed into the bloodstream and subsequently oxidized to TMAO by hepatic flavin-containing monooxygenase enzymes.

Elevated circulating TMAO levels have been associated with an increased risk of CAD and adverse cardiovascular events. Mechanistically, TMAO is thought to promote atherosclerosis through several pathways. It has been shown to enhance cholesterol accumulation in macrophages, leading to the formation of foam cells, a hallmark of early atherosclerotic lesions. Additionally, TMAO has been implicated in impairing reverse cholesterol transport, a process crucial for removing excess cholesterol from peripheral tissues. TMAO also promotes platelet hyperresponsiveness, thereby increasing the likelihood of thrombotic events. Furthermore, TMAO has been linked to endothelial dysfunction, inflammation, and oxidative stress, all of which contribute to atherosclerosis progression.

Short-chain fatty acids are another group of microbial metabolites that have garnered attention due to their potential cardioprotective effects. SCFAs, such as acetate, propionate, and butyrate, are produced through the fermentation of dietary fiber by gut bacteria. They play a role in maintaining gut barrier integrity, modulating immune responses, and exerting anti-inflammatory effects [4,5].

SCFAs can influence systemic inflammation by interacting with immune cells and modulating their activation. These anti-inflammatory properties may indirectly impact CAD by reducing the overall burden of chronic inflammation, which is a key driver of atherosclerosis. Bile acids, primarily known for their role in lipid digestion and absorption, also have implications for CAD. The gut microbiota play a crucial role in bile acid metabolism by deconjugating and transforming primary bile acids into secondary bile acids. Bile acids can act as signaling molecules through activation of various nuclear receptors, such as the farnesoid X receptor and the G-protein-coupled bile acid receptor 1.

The interplay between bile acids, the gut microbiome, and CAD is complex. FXR activation by bile acids can influence lipid and glucose metabolism, impacting systemic metabolic health. TGR5 activation has been associated with improved glucose homeostasis and anti-inflammatory effects. Dysregulation of bile acid metabolism has been observed in metabolic disorders, including obesity and diabetes, which are significant risk factors for CAD.

Immune system modulation

The gut microbiome plays a pivotal role in shaping the host's immune system. Dysbiosis can lead to a state of chronic inflammation, contributing to atherosclerosis progression. Gut microbes can activate immune cells and produce inflammatory mediators that promote endothelial dysfunction and plaque formation. Conversely, a balanced gut microbiome composition is associated with anti-inflammatory effects that can mitigate CAD risk. Understanding the gut-heart axis has opened doors to potential therapeutic interventions for CAD. Modulating the gut microbiome through probiotics, prebiotics, dietary modifications, and fecal microbiota transplantation holds promise for reducing CAD risk. Targeting specific microbial species or pathways involved in metabolite production could provide novel strategies for CAD prevention and treatment.

Conclusion

The gut-heart axis represents a fascinating avenue of research with significant implications for CAD prevention and management. The gut microbiome's role in modulating metabolism, inflammation, and immune responses underscores its potential influence on CAD development and progression. As our understanding deepens, microbiome-based interventions could revolutionize how we approach CAD, offering innovative strategies to complement traditional therapies and improve cardiovascular outcomes.

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