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The gut microbiome and hypertension

Nature Reviews Nephrology volume 19, pages 153–167 (2023)Cite this article

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Abstract

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, 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.

Key points

  • Clinical and experimental evidence show 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 to 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.

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Fig. 1: Effect of food on BP regulation via the gut microbiome and their metabolites.
Fig. 2: Bacterial load, oxygen, SCFAs and pH throughout the intestine.
Fig. 3: Gut epithelial barrier in hypertension.

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Acknowledgements

J.A.O. is supported by a National Health and Medical Research Council Early Career Fellowship (1124288). F.Z.M. is supported by a Senior Medical Research Fellowship from the Sylvia and Charles Viertel Charitable Foundation Fellowship and a National Heart Foundation Future Leader Fellowship (105663). G.M. is partially supported by NHMRC grant GNT2013468.

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Author notes

  1. These authors contributed equally: Joanne A. O’Donnell, Tenghao Zheng.

Authors and Affiliations

  1. Hypertension Research Laboratory, School of Biological Sciences, Faculty of Science, Monash University, Melbourne, Victoria, Australia

    Joanne A. O’Donnell, Tenghao Zheng & Francine Z. Marques

  2. Cambridge-Baker Systems Genomics Initiative, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Guillaume Meric

  3. Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Victoria, Australia

    Francine Z. Marques

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All authors researched data for the article, made substantial contributions to discussions of the content and wrote, reviewed or edited the manuscript before submission.

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Related links

Genome Taxonomy Database: https://gtdb.ecogenomic.org/

Glossary

Colonization resistance

The ability of the commensal microbiota to limit the expansion of pathogens and exogenous microorganisms.

Coprophagy

The ingestion of faeces; in this context by rodents.

Interstitial cells of Cajal

Mesenchymal cells located in the intestine that mediate contractility.

Microfold (M) cells

Specialized intestinal cells, located in the Peyer’s patches and other mucosa-associated lymphoid tissues, which sample pathogens or antigens from the intestinal lumen to the sub-epithelium.

Tuft cells

Chemosensory cells located in the gut epithelial layer.

Zero-inflation

Microbiome data typically contain several taxa (metagenome-assembled genomes or operational taxonomic units) that are only present in some samples, resulting in many taxa with zero counts.

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O’Donnell, J.A., Zheng, T., Meric, G. et al. The gut microbiome and hypertension. Nat Rev Nephrol 19, 153–167 (2023). https://doi.org/10.1038/s41581-022-00654-0

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