Gut Microbial Metabolites and Blood Pressure Regulation: Focus on SCFAs and TMAO

Abstract

Shifts in the gut microbiome play a key role in blood pressure regulation, and changes in the production of gut microbial metabolites are likely to be a key mechanism. Known gut microbial metabolites include short-chain fatty acids, which can signal via G-protein-coupled receptors, and trimethylamine-N oxide. In this review, we provide an overview of gut microbial metabolites documented thus far to play a role in blood pressure regulation.

Keywords: G-protein-coupled receptors; blood pressure; gut microbial metabolite; hypertension.

FIGURE 1.

Mechanisms and sites of microbial SCFA-mediated blood pressure regulation Production of short-chain fatty acids (SCFAs) in the gut leads to absorption in the distal gut through diffusion and active transport. SCFAs then travel through the circulation to activate receptors in the kidney, brain, sympathetic nervous system, vasculature, and heart, leading to blood pressure effects. (*Note: Olr59 is the rat ortholog of Olfr78.) Although each organ system shows known receptor expression, these effects have not all been proven to be due to receptor activation. Acetate, propionate, and butyrate are all ligands for Gpr41 and Gpr43, whereas acetate and propionate activate Olfr78. Butyrate acts on Olfr558 and Gpr109a. Niacin can also activate GPR109a. Activation of these GPCRs leads to downstream effects that are yet to be elucidated.