The gut microbiome and hypertension

A large body of evidence has emerged in the past decade supporting the role of 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 signaling pathways via G protein-coupled receptors or through direct immune cell activation. Moreover, dysbiosis-associated 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.

• Clinical and experimental evidence shows that changes in the gut microbiome are associated with and might lead to changes in blood pressure.
• Metabolites produced by the gut microbiota are key mediators of the host–microbiota relationship that can drive changes in blood pressure; these metabolites can have immune-dependent and -independent effects.
• Gut microbial-derived metabolites can be beneficial (for example, short-chain fatty acids, indole-3-lactic acid, arachidonic acid) or detrimental (for example, trimethylamine N-oxide) to blood pressure regulation.
• Experimental hypertension is associated with disruption of the gut epithelial barrier and intestinal mechanotransduction; these might contribute to hypertension.
• Gut microbiome modulation might represent a therapeutic approach to lowering blood pressure, for example, through the oral delivery of gut microbial metabolites such as short-chain fatty acids.
• Addressing important challenges to gut microbiome research in the hypertension field, such as confounding factors, causality, and global action to improve the diversity of samples, will accelerate discovery and translation.
   

References

O'Donnell JA, Zheng T, Meric G, Marques FZ. The gut microbiome and hypertension. Nat Rev Nephrol. 2023 Mar;19(3):153-167. doi: 10.1038/s41581-022-00654-0. Epub 2023 Jan 11. PMID: 36631562.