The gut microbiome and hypertension

A large body of evidence has emerged in the past decade supporting a role for the gut microbiome in the regulation of blood pressure. The field has moved from association to causation in the last 5 years, with studies that have used germ-free animals, antibiotic treatments and direct supplementation with microbial metabolites. The gut microbiome can regulate blood pressure through several mechanisms, including through gut dysbiosis-induced changes in microbiome-associated gene pathways in the host. Microbiota-derived metabolites are either beneficial (for example, short-chain fatty acids and indole-3-lactic acid) or detrimental (for example, trimethylamine N-oxide), and can activate several downstream signalling pathways via G protein-coupled receptors or through direct immune cell activation. Moreover, dysbiosisassociated breakdown of the gut epithelial barrier can elicit systemic inflammation and disrupt intestinal mechanotransduction. These alterations activate mechanisms that are traditionally associated with blood pressure regulation, such as the renin-angiotensin-aldosterone system, the autonomic nervous system, and the immune system. Several methodological and technological challenges remain in gut microbiome research, and the solutions involve minimizing confounding factors, establishing causality and acting globally to improve sample diversity. New clinical trials, precision microbiome medicine and computational methods such as Mendelian randomization have the potential to enable leveraging of the microbiome for translational applications to lower blood pressure.

Automated summary

A large body of evidence has shown that the gut microbiome plays a role in regulating blood pressure through various mechanisms, including changes in gene pathways and the production of beneficial or detrimental metabolites. Dysbiosis in the gut microbiome can result in inflammation and disruption of the intestinal barrier, activating mechanisms associated with blood pressure regulation. Challenges in gut microbiome research include minimizing confounding factors and establishing causality, but new approaches such as clinical trials and computational methods offer potential for leveraging the microbiome to lower blood pressure.