Gut microbiota: a promising target against cardiometabolic diseases

ABSTRACT

Introduction: Cardiometabolic diseases (CMD) are a group of interrelated disorders such as metabolic syndrome, type 2 diabetes mellitus and cardiovascular diseases (CVD). As the prevalence of these diseases increases globally, efficient new strategies are necessary to target CMD and modifiable risk factors. In the past decade, evidence has accumulated regarding the influence of gut microbiota (GM) on CMD, providing new targets for therapeutic interventions.

Areas covered: This narrative review discusses the pathophysiologic link between CMD, GM, and potential microbiota-based targets against atherosclerosis and modifiable risk factors for atherosclerosis. Low-grade inflammation can be induced through GM and its derived metabolites. CMD are influenced by GM and microbiota-derived metabolites such as short-chain fatty acids (SCFA), secondary bile acids, trimethylamine N-oxide (TMAO), and the composition of GM can modulate host metabolism. All of the above can lead to promising therapeutic targets.

Expert opinion: Most data are derived from animal models or human association studies; therefore, more translational and interventional research in humans is necessary to validate these promising findings. Reproduced findings such as aberrant microbiota patterns or circulating biomarkers could be targeted depending on individual metabolic profiles, moving toward personalized medicine in CMD.

KEYWORDS:

• Gut microbiome
• cardiovascular diseases
• metabolic diseases
• inflammation
• drug therapy

Article highlights

• Gut microbiota (GM) are involved in inducing low-grade inflammation which contributes to the development of cardiometabolic diseases (CMD).

• CMD such as metabolic syndrome (MS), type 2 diabetes mellitus (T2DM), and atherosclerosis can be induced by GM-derived metabolites in animal models.

• Several GM-derived metabolites influence CMD such as short-chain fatty acids (SCFA), secondary bile acids, and trimethylamine N-oxide (TMAO). CMD are associated with GM dysbiosis, characterized by altered GM diversity and composition.

• Atherosclerosis and factors involved in the development of atherosclerosis such as low-grade inflammation, MS and T2DM may be therapeutically targeted by influencing GM.

• Novel strategies targeting GM to prevent or treat atherosclerosis include altering the production of SCFA, intermediates of secondary bile acid metabolism and TMAO. Current and potential initiatives to achieve this, e.g. using novel drugs or probiotics, will be discussed.

Declaration of interest

MV Warmbrunn is an owner of Nature Plus. M Nieuwdorp is a member of the scientific advisory board of Caelus Health. MV Warmbrunn is supported by a CVON In control grant (2018-27). M Nieuwdorp is supported by a ZONMW VIDI grant 2013 (016.146.327). Icons for figures were provided by Les Laboratoires Servier, the SMART (Servier Medical ART) image collection (https://smart.servier.com/). 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

M Nieuwdorp is supported by a ZONMW VIDI grant 2013 (016.146.327) and a CVON consortium grant INCONTROL 2 (2018-27), on which MV Warmbrunn is appointed. J Aron-Wisnewsky is supported by the Bettencourt Schueller research grant.