Gut Microbiome and Response to Cardiovascular Drugs

Abstract

The gut microbiome is emerging as an important contributor to both cardiovascular disease risk and metabolism of xenobiotics. Alterations in the intestinal microbiota are associated with atherosclerosis, dyslipidemia, hypertension, and heart failure. The microbiota have the ability to metabolize medications, which can results in altered drug pharmacokinetics and pharmacodynamics or formation of toxic metabolites which can interfere with drug response. Early evidence suggests that the gut microbiome modulates response to statins and antihypertensive medications. In this review, we will highlight mechanisms by which the gut microbiome facilitates the biotransformation of drugs and impacts pharmacological efficacy. A better understanding of the complex interactions of the gut microbiome, host factors, and response to medications will be important for the development of novel precision therapeutics for targeting CVD.

Keywords: atherosclerosis; hypertension; metabolomics; microbiota; pharmacogenetics; pharmacokinetics; pharmacologic actions.

Figure 1.

Mechanisms by which the gut microbiome influence drug response. A. The gut microbiota produce enzymes that can directly metabolize drugs via biochemical reactions (acetylation, β-glucuronidation, deconjugation, dihydroxylation, denitration, hydrolysis, reduction, etc) interfering with drug pharmacokinetics. These reactions can biotransform prodrugs to activate metabolites, inactive compounds or lead to the formation of toxic metabolites. B. The gut microbiota can indirectly influence response to medication by the generation of microbial metabolites that can compete with host transport or detoxification systems, impact host receptor signaling pathways and alter host gene expression. Additional opportunities for microbiome-drug interactions exist for medications that undergo biliary excretion.