Scientific Summary: Role of Specific Gut Bacteria in Coronary Artery Disease (CAD) Introduction

Scientific Summary: Role of Specific Gut Bacteria in Coronary Artery Disease (CAD) Introduction

 Introduction

 Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide, and its pathogenesis is closely linked to atherosclerosis—a chronic, progressive, inflammatory disease of the arteries. Recent research has underscored the pivotal role of gut microbiota in the development and progression of CAD. The gut microbiome, composed of trillions of microorganisms, plays a critical role in maintaining physiological balance, influencing immune function, and regulating metabolic processes. Dysbiosis, or the imbalance in gut microbiota, has been associated with various diseases, including CAD, through complex mechanisms involving inflammation, metabolite production, immune modulation, and lipid metabolism.

Key Gut Bacteria Involved in CAD

The gut microbiota is a highly diverse community, with specific bacterial species and genera identified as key players in the pathogenesis of CAD. Below is a detailed discussion of some of the most studied bacterial taxa:

  1. Bacteroidetes and Firmicutes: A decrease in Bacteroidetes and an increase in Firmicutes have been observed in patients with CAD. This imbalance is thought to contribute to metabolic disturbances that promote atherogenesis​(PubMed,BioMed Central).
  1. Blautia: The genus Blautia has been positively associated with markers of heart dysfunction, including creatine kinase and C-reactive protein (CRP), which are involved in inflammatory processes contributing to CAD. Blautiaspp. are known to be involved in carbohydrate fermentation, producing short-chain fatty acids (SCFAs) that can influence systemic inflammation​(BioMed Central).
  1. Collinsella: Collinsella spp. have been found to be elevated in CAD patients. These bacteria are involved in cholesterol metabolism and have been linked to increased production of pro-inflammatory metabolites, which may exacerbate atherosclerosis​(Frontiers).
  1. Rothia and Eubacterium: Decreased levels of Rothia and Eubacterium spp. have been reported in CAD patients. These genera are generally associated with anti-inflammatory effects, and their reduction may contribute to the heightened inflammatory state observed in CAD​(Frontiers).
  1. Bifidobacterium: This genus is typically considered beneficial, with anti-inflammatory properties and a role in maintaining gut barrier integrity. However, its levels are often reduced in CAD patients, potentially contributing to increased gut permeability and systemic inflammation​(Frontiers).
  1. Faecalibacterium: Known for its anti-inflammatory properties, particularly through the production of butyrate, Faecalibacterium spp. are often depleted in CAD patients, leading to a reduction in protective anti-inflammatory effects​(BioMed Central).
  1. Akkermansia: Akkermansia muciniphila is another beneficial bacterium that helps maintain gut barrier function. Its reduction in CAD patients may lead to increased endotoxemia, promoting systemic inflammation and atherogenesis​(BioMed Central,Frontiers).
  1. Rikenellaceae and Coprobacter: These genera have been identified as potential biomarkers for CAD, with alterations in their abundance correlating with disease severity. Their exact roles in CAD pathogenesis are still under investigation, but they may influence host metabolism and immune responses​(BioMed Central).

Mechanisms of Gut Microbiota in CAD Pathogenesis

The gut microbiota influences CAD through several key mechanisms:

  1. Metabolite Production: Gut bacteria produce various metabolites, such as short-chain fatty acids (SCFAs), trimethylamine (TMA), and secondary bile acids, which have systemic effects. TMA is converted in the liver to trimethylamine-N-oxide (TMAO), a metabolite strongly associated with atherosclerosis. TMAO enhances cholesterol deposition in arterial walls, promotes foam cell formation, and increases platelet reactivity, all of which contribute to atherogenesis​(PubMed,BioMed Central).
  1. Inflammation: Dysbiosis leads to increased gut permeability, allowing bacterial components such as lipopolysaccharides (LPS) to enter the bloodstream. LPS is a potent endotoxin that triggers systemic inflammation by activating toll-like receptors (TLRs) on immune cells. This chronic low-grade inflammation is a key driver of atherosclerosis and CAD​(PubMed,BioMed Central).
  1. Immune Modulation: Gut bacteria can modulate the host’s immune system, either by promoting pro-inflammatory or anti-inflammatory responses. For example, certain bacteria like Bifidobacterium and Lactobacillus are known to enhance regulatory T cell (Treg) responses, which are protective against inflammation. Conversely, bacteria like Collinsella may promote pro-inflammatory responses that exacerbate atherosclerosis​(Frontiers).
  1. Lipid Metabolism: The gut microbiota influences lipid metabolism by affecting bile acid metabolism and the enterohepatic circulation of cholesterol. Dysbiosis can lead to alterations in bile acid profiles, affecting cholesterol absorption and lipid homeostasis, thus promoting atherogenesis​(PubMed,Frontiers).
  1. Endothelial Dysfunction: The interaction between gut microbiota and the host can lead to endothelial dysfunction, a precursor to atherosclerosis. This is mediated through inflammatory cytokines, oxidative stress, and the direct effects of metabolites like TMAO on endothelial cells, leading to impaired vasodilation and increased vascular stiffness​(BioMed Central,Frontiers).

Therapeutic Implications

Understanding the role of gut microbiota in CAD opens new avenues for therapeutic interventions. Probiotics, prebiotics, and dietary interventions aimed at restoring healthy gut microbiota balance hold promise for preventing or mitigating CAD. Additionally, targeting specific metabolites like TMAO through dietary modifications or pharmacological agents could provide a novel approach to reducing CAD risk​(PubMed,BioMed Central).

Moreover, fecal microbiota transplantation (FMT) is being explored as a potential therapy to correct dysbiosis in CAD patients. However, more research is needed to fully understand the long-term effects and safety of such interventions​(BioMed Central).

Conclusion

The gut microbiota plays a crucial role in the pathogenesis of coronary artery disease through various mechanisms, including metabolite production, immune modulation, inflammation, and lipid metabolism. Specific bacterial genera, such as Blautia, Collinsella, and Bifidobacterium, have been identified as key players in CAD. Therapeutic strategies targeting the gut microbiota offer promising potential for preventing and managing CAD, though further research is required to fully elucidate these relationships and develop effective interventions.

References

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  2. Zhang B, Wang X, Xia R, et al. Gut microbiota in coronary artery disease: a friend or foe? Biosci Rep. 2020;40(5)

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