Role of the microbiota in hypertension and antihypertensive drug metabolism

Recent evidence suggests that the gut microbiota plays an important role in the development and pathogenesis of hypertension. Dysbiosis, an imbalance in the composition and function of the gut microbiota, was shown to be associated with hypertension in both animal models and humans. In this review, we provide insights into host-microbiota interactions and summarize the evidence supporting the importance of the microbiota in blood pressure (BP) regulation. Metabolites produced by the gut microbiota, especially short-chain fatty acids (SCFAs), modulate BP and vascular responses. Harmful gut-derived metabolites, such as trimethylamine N-oxide and several uremic toxins, exert proatherosclerotic, prothrombotic, and proinflammatory effects. High-salt intake alters the composition of the microbiota, and this microbial alteration contributes to the pathogenesis of salt-sensitive hypertension. In addition, the microbiota may impact the metabolism of drugs and steroid hormones in the host. The drug-metabolizing activities of the microbiota affect the pharmacokinetic parameters of antihypertensive drugs and contribute to the pathogenesis of licorice-induced pseudohyperaldosteronism. Furthermore, the oral microbiota plays a role in BP regulation by producing nitric oxide, which lowers BP via its vasodilatory effects. Thus, antihypertensive intervention strategies targeting the microbiota, such as the use of prebiotics, probiotics, and postbiotics (e.g., SCFAs), are considered new therapeutic options for the treatment of hypertension.