Korean Circ J.  2023 Aug;53(8):499-518. 10.4070/kcj.2023.0048.

The Gut-Heart Axis: Updated Review for The Roles of Microbiome in Cardiovascular Health

• Bui TVA
• Hwangbo H
• Lai Y
• Hong SB
• Choi YJ
• Park HJ
• Ban K

• KMID: 2545148
• DOI: http://doi.org/10.4070/kcj.2023.0048

Abstract

Cardiovascular diseases (CVDs), including coronary artery disease, stroke, heart failure, and hypertension, are the global leading causes of death, accounting for more than 30% of deaths worldwide. Although the risk factors of CVDs have been well understood and various treatment and preventive measures have been established, the mortality rate and the financial burden of CVDs are expected to grow exponentially over time due to the changes in lifestyles and increasing life expectancies of the present generation. Recent advancements in metagenomics and metabolomics analysis have identified gut microbiome and its associated metabolites as potential risk factors for CVDs, suggesting the possibility of developing more effective novel therapeutic strategies against CVD. In addition, increasing evidence has demonstrated the alterations in the ratio of Firmicutes to Bacteroidetes and the imbalance of microbial-dependent metabolites, including short-chain fatty acids and trimethylamine N-oxide, play a crucial role in the pathogenesis of CVD. However, the exact mechanism of action remains undefined to this day. In this review, we focus on the compositional changes in the gut microbiome and its related metabolites in various CVDs. Moreover, the potential treatment and preventive strategies targeting the gut microbiome and its metabolites are discussed.

Keyword

Cardiovascular diseases; Microbiome; Short-chain fatty acid; Microbial-dependent metabolites; Trimethylamine N-oxide

Figure

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  Figure 1 Major signaling pathways of gut microbiome metabolites contributing to CVDs. SCFAs released by the gut microbiome can enter various cell types to inhibit HDAC and NF-κB, suppressing pro-inflammatory and enhancing anti-inflammation gene expression. In contrast, TMAO which is produced from trimethylamine triggers inflammation reactions, exacerbating CVDs.CVD = cardiovascular disease; FMO = flavin-containing monooxygenase; GPCR = G-protein coupled receptor; GRP = glucose regulated protein; HDAC = histone deacetylase; HSP = heat shock protein; IL = interleukin; INF = interferon; MAPK = mitogen-activated protein kinase; NF-κB = nuclear factor kappa B; NLRP3 = NLR family pyrin domain containing 3; SCFA = short-chain fatty acid; TMA = trimethylamine; TMAO = trimethylamine N-oxide; TNF = tumor necrosis factor.

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  Figure 2 Modulation gut microbiome approaches in cardiovascular disease treatment and prevention. Prebiotic consumption, fecal microbiota transplantation, and engineered bacteria administration can be employed to maintain healthy gut microbiome or to improve unbalanced microbiome, leading to systemic effects on the cardiovascular system and improving cardiovascular health.

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