The human gut microbiome – a new and exciting avenue in cardiovascular drug discovery

ABSTRACT

Introduction: Over the past decade, numerous research efforts have identified the gut microbiota as a novel regulator of human metabolic syndrome and cardiovascular disease (CVD). With the elucidation of underlying molecular mechanisms of the gut microbiota and its metabolites, the drug-discovery process of CVD therapeutics might be expedited.

Areas covered: The authors describe the evidence concerning the impact of gut microbiota on metabolic disorders and CVD and summarize the current knowledge of the gut microbial mechanisms that underlie CVD with a focus on microbial metabolites. In addition, they discuss the potential impact of the gut microbiota on the drug efficacy of available cardiometabolic therapeutic agents. Most importantly, the authors review the role of the gut microbiome as a promising source of potential drug targets and novel therapeutics for the development of new treatment modalities for CVD. This review also presents the various effective strategies to investigate the gut microbiome for CVD drug-discovery approaches.

Expert opinion: With the elucidation of its causative role in cardiometabolic disease and atherosclerosis, the human gut microbiome holds promises as a reservoir of novel potential therapeutic targets as well as novel therapeutic agents, paving a new and exciting avenue in cardiovascular drug discovery.

KEYWORDS:

• Gut microbiome
• cardiovascular disease
• atherosclerosis
• drug targets
• drug discovery

Article highlights

• A large body of evidence indicates that gut dysbiosis is implicated in cardiovascular disease (CVD) as well as many aspects of cardiometabolic syndrome.

• The gut microbiota produces or modifies host produced small-molecule metabolites, such as trimethylamine-N-oxide, short-chain fatty acids and secondary bile acids, that can act locally or systematically to affect CVD pathogenesis.

• The gut microbiota has the potential to modulate drug efficacy and metabolism, while drugs may exert their effects on CVD via modulating the gut microbiota.

• The gut microbiota provides potential novel drug targets for CVD drug discovery, exemplified by targeting microbial TMA-producing enzymes CutC/D.

• The gut microbiome is a reservoir of novel therapeutics ranging from small molecules to live microbes for drug discovery in CVD.

• Integrating metagenomic mining together with other omic technologies as well as synthetic biology will benefit the exploration of new targets or metabolites from human gut microbiome for CVD drug discovery.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by grants from the National Natural Science Foundation of China [81402929, 81473214, 81621064, 81630089, 81703398 and 81872780], CAMS Innovation Fund for Medical Sciences [2016-I2M-1-011, 2017-I2M-1-008, 2016-I2M-2-002 and 2018-I2M-3-005], the Drug Innovation Major Project [2018ZX09711001-007, 2018ZX09711001-006, and 2018ZX09711001-003] and Beijing Natural Science Foundation [7162129].