Review articleInteraction between gut microbiome and cardiovascular disease
Introduction
Cardiovascular diseases (CVDs), including atherosclerosis, hypertension, heart failure, atrial fibrillation and myocardial fibrosis, are associated with high morbidity and mortality. Many risk factors are widely known, such as smoking, poor dietary habits, obesity, diabetes mellitus and high cholesterol [1], but these cannot explain all CVD incidences. Recent studies focus our attention on the interaction between gut microbiome and CVD [2,3]. Accumulating evidence has demonstrated that gut microbiome and their metabolites play a pivotal role in the onset and progression of CVD. The oral microbiome can affect gut microbiota composition and also contribute to these diseases [4].
The human gastrointestinal tract can be considered an enormous and diverse ecosystem, which houses trillions of microbial communities secreting metabolites [5]. Specific diet and ingestion of prebiotics and probiotics bring beneficial effects in optimizing community structure [6,7]. The main metabolites of gut microbiota include trimethylamine-N-oxide (TMAO) and short-chain fatty acids (SCFAs). The positive correlation of TMAO on the prediction of cardiovascular risk has been demonstrated, even after the adjustment of traditional risk factors [8]. In contrast, SCFA is beneficial for blood pressure control.
In this review, we will focus on discussing the metabolism of TMAO, the role of gut microbiome and their main metabolites, specifically TMAO, in the pathogenesis of CVD and the novel therapeutic strategy that may result from targeting these factors. We also briefly introduce the beneficial role of SCFA in CVD.
Section snippets
TMAO
The human gut is colonized by approximately 100 trillion bacteria, which influence the physiology and metabolism of the body [9]. When large quantities of choline, carnitine and phosphatidylcholine are ingested, specific intestinal bacterial degrade them into the precursor Trimethylamine (TMA) [10]. Gut microbiota can use these nutrients as a carbon fuel source by releasing TMA under the action of TMA lyases, which can cleave the C
N bond of nutrients [11] (Fig. 1). This process involves two
Intestinal microbiome in coronary heart disease
TMAO is a cardiovascular risk predictor that correlates with atherosclerosis in many clinical studies [27]. The incidence of cardiovascular events increases with the elevated levels of TMAO in patients with acute coronary syndrome whose troponin T is negative [22]. Levels of TMAO also predict 5-year mortality in patients with stable coronary artery disease [28]. Recently, a study reported a clear relationship between serum TMAO concentration and coronary atherosclerosis in chronic kidney
New potential therapeutic target in CVD
Targeting gut microbiota and metabolites is becoming a novel and attractive field in the treatment of CVD. Specific bacteria including Anaerococcus hydrogenalis, Clostridium asparagiforme, Clostridium hathewayi, Clostridium sporogenes, Escherichia fergusonii, Proteus penneri, Providencia rettgeri, and Edwardsiella tarda are deemed to contribute to the production of TMAO from TMA in vitro [61]. Targeting bacteria that give rise to TMAO could represent an attractive strategy to treat
Conclusions and perspective
The current studies demonstrate that gut microbiota and its metabolites, especially TMAO, play an important role in the onset and progress of CVD. Therapies targeting the gut microbiota and metabolites, including prebiotic and probiotics, Archaea, DMB, FMT, and FMO3 inhibitors, present new strategies for treating CVD. However, existing research in this field is just a tip of the iceberg. There is still a big step needed to further understand the molecular and genetic mechanisms of the gut
Acknowledgement
This work received financial support from the National Natural Science Foundation of China (No. 81470256).
Conflicts of interest
The authors declare no conflict of interest.
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