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Gut Microbiome and Cardiovascular Diseases

Discussion in 'Cardiology' started by Valery1957, Feb 15, 2020.

  1. Valery1957

    Valery1957 Famous Member

    Jan 10, 2019
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    Gut Microbiome and Cardiovascular Diseases
    Naofumi Yoshida, Tomoya Yamashita,* and Ken-ichi Hirata
    Luis Vitetta, Academic Editor
    Author information Article notes Copyright and License information Disclaimer
    This article has been cited by other articles in PMC.

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    Recent evidence has suggested that the gut microbiome is involved in human health and diseases, such as inflammatory bowel disease, liver cirrhosis, rheumatoid arthritis, and type 2 diabetes. Cardiovascular diseases, which are associated with high morbidity and mortality across the world, are no exception. Increasing evidence has suggested a strong relationship between the gut microbiome and the progression of cardiovascular diseases. We first reported such a relationship with coronary artery disease two years ago. Next-generation sequencing techniques, together with bioinformatics technology, constantly and dramatically expand our knowledge of the complex human gut bacterial ecosystem and reveal the exact role of this bacterial ecosystem in cardiovascular diseases via the functional analysis of the gut microbiome. Such knowledge may pave the way for the development of further diagnostics and therapeutics for prevention and management of cardiovascular diseases. The aim of the current review is to highlight the relationship between the gut microbiome and their metabolites, and the development of cardiovascular diseases by fostering an understanding of recent studies.

    Keywords: gut microbiome, cardiovascular diseases, Bacteroides
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    1. Introduction
    The human gastrointestinal tract harbors several hundred trillion bacteria that are collectively referred to as the gut microbiome, which is called the “forgotten organ” because of its important roles beyond digestion and metabolism [1,2]. Growing evidence suggests that the gut microbiome is associated with the pathogenesis of both intestinal and extra-intestinal disorders, such as obesity and other related metabolic diseases, inflammatory bowel disease, and non-alcoholic steatohepatitis, among others [3,4,5]. Next-generation sequencing techniques and multi-omics approaches have constantly and dramatically expanded our knowledge of the microbial world. A new era is dawning with the recognition of the gut microbiome as a “multifunctional organ”. Unsurprisingly, cardiovascular diseases (CVDs) are no exception to this association [6].

    CVDs are the leading causes of mortality and morbidity in many developed and developing countries, despite the widespread use of medical therapy in the last decade [7,8,9]. CVDs are responsible for 17.7 million deaths every year (31% of all global deaths), including one of every three deaths in the United States and one of every four deaths in Europe and Japan [8]. By 2030, 40.5% of the US population is projected to have some form of CVD. Between 2010 and 2030, the real, total direct medical costs of CVD are predicted to triple from $273 billion to $818 billion, and the real, indirect costs (owing to lost productivity) for all CVDs are estimated to increase by 61% ($172 billion to $276 billion) [10]. These data strongly support the idea that effective and inexpensive prevention and therapeutic strategies are needed for patients with CVDs. The gut microbiome contributes to human metabolism and the immune system, and is being currently investigated as a diagnostic and therapeutic target for CVDs. Thus, the aim of this review is to discuss the evidence for the relationship between the gut microbiome and CVDs to promote an understanding of the latest perspectives of the role of the gut microbiome in CVDs. Moreover, we have raised several issues that should be considered when interpreting previous evidence.

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    2. Trimethylamine-N-oxide and CVDs
    A close relationship between the gut microbe-dependent production of trimethylamine-N-oxide (TMAO), derived from specific dietary nutrients such as choline and carnitine, and future cardiovascular events has been widely recognized [10]. Trimethylamine (TMA), which is produced by the gut microbial enzymes TMA lyases, is a precursor of TMAO. TMAO can be measured by liquid chromatography-mass spectrometry. Elevated blood TMAO levels have been directly linked to poor outcomes in patients with CVDs, such as coronary artery disease and acute and chronic heart failure (Table 1) [11,12,13,14,15,16]. Tang et al., investigated the relationship between the fasting plasma levels of TMAO and the incidence of major adverse cardiovascular events (death, myocardial infarction, or stroke) during three years of follow-up in 4007 patients undergoing elective cardiac catheterization [13]. They found that the patients in the highest quartile for circulating TMAO levels had a 2.5-fold increased risk of major adverse cardiovascular events, compared with the patients with values in the lowest quartile. Of note, even after adjustment for traditional risk factors, an elevated TMAO level could predict an increased risk of major adverse cardiovascular events [13]. Additionally, high TMAO levels were observed in patients with stable heart failure compared to healthy subjects [11]. This result suggests that the gut microbiome may play a role in the development and progression of heart failure. They also showed that elevated TMAO levels were associated with a 2.2-fold increase in the risk of mortality, after an adjustment for traditional risk factors and the brain natriuretic peptide. Moreover, the blood TMAO levels were associated with coronary plaque vulnerability, as assessed by optical coherence tomography, and the long-term risks of cardiovascular events in patients with acute coronary syndrome [14]. The latest metagenome-wide association study demonstrated the microbial characterization of coronary artery disease (CAD) patients and showed that the gut microbial enzymes that produce TMA were enriched in the patients with CAD compared to the healthy controls [17].

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