Pharmacomicrobiomics: Exploiting the Drug-Microbiota Interactions in Antihypertensive Treatment

Abstract

Hypertension is a leading risk factor for cardiovascular diseases and can reduce life expectancy. Owing to the widespread use of antihypertensive drugs, patients with hypertension have improved blood pressure control over the past few decades. However, for a considerable part of the population, these drugs still cannot significantly improve their symptoms. In order to explore the reasons behind, pharmacomicrobiomics provide unique insights into the drug treatment of hypertension by investigating the effect of bidirectional interaction between gut microbiota and antihypertensive drugs. This review discusses the relationship between antihypertensive drugs and the gut microbiome, including changes in drug pharmacokinetics and gut microbiota composition. In addition, we highlight how our current knowledge of antihypertensive drug-microbiota interactions to develop gut microbiota-based personalized ways for disease management, including antihypertensive response biomarker, microbial-targeted therapies, probiotics therapy. Ultimately, a better understanding of the impact of pharmacomicrobiomics in the treatment of hypertension will provide important information for guiding rational clinical use and individualized use.

Keywords: antihypertensive drugs; gut microbiota; interaction; pharmacomicrobiomics; precision medicine.

Figure 1

Interactions between drugs and gut microbiome (GM). In the intestinal tract, there are complex interactions between drugs and microorganisms. On the one hand, drugs can result in alterations in the composition and function of gut microbiome. On the other hand, gut microbiome may alter chemical structure of drugs, and directly or indirectly affect drug efficacy. TMAO, trimethylamine N-oxide; SCFA, short-chain fatty acids. Arrow mark indicates Drugs, GM metabolites and drug ingredients after GM transformation are transferred outside the gut.

Figure 2

The influence of gut microbiome on the metabolism of antihypertensive drugs. (A) Oxidation of amlodipine. Amlodipine is converted into dehydroamlodipine through the oxidation reaction of gut microbiome. (B) Oxidation of nifedipine. Biotransformation of nifedipine produces dehydronifedipine through gut microbiome. (C) Deacetylation of diltiazem. Diltiazem is converted into desacetyldiltiazem through the action of gut microbiome. (D) Deglucuronidation of losartan. Losartan is converted into losartan N2-glucuronide through the action of gut microbiome. (E) De-esterification of enalapril. Enalapril is converted into enalaprilat through the de-esterification reaction of gut microbiome.