Gut Microbiota in Hypertension

Pedro A. Jose; Dominic Raj


Curr Opin Nephrol Hypertens. 2015;24(5):403-409. 

In This Article

Gut Microbiota, Genetics, Hypertension, and Salt Sensitivity

The gut microbiota is influenced not only by nutrition and environment but also by genetic factors.[91,92] The gut microbiota can modify the expression of the hypertensive phenotype in mice with germ-line deletion of Slc26a6, which encodes an anion exchanger, Olfr78, which encodes an olfactory receptor, or toll-like receptor 5 (Tlr5), a gene component of the innate immune system expressed in the gut mucosa.[42–44] Dietary nutrients have also been reported to affect microRNA (miR) and DNA methylation and acetylation, and affect blood pressure. The biological function of probiotics has been suggested to be a consequence of epigenetic modification.[93]

As already mentioned, the increase in blood pressure with an increase in sodium intake occurs in normotensive as well as hypertensive humans and is predictive of increased cardiovascular events and mortality, irrespective of basal blood pressure levels.[10,11] The mechanisms underlying salt sensitivity are not well understood.[94–98] However, genetics can determine the blood pressure response to salt intake.[31,99–105] We have recently reported that intronic variants [intron 22–23 (rs7571842) and intron 25–26 (rs1017783)] of solute carrier family 4 (sodium bicarbonate cotransporter), member 5 (SLC4A5) and G protein-coupled receptor kinase 4 (GRK4 65R>L rs2960306) are associated with salt sensitivity in two Euro-American populations.[99] GRK4 is important in the regulation of the dopamine receptors and, as mentioned above, dopamine receptors are important in the regulation of renal sodium transport and blood pressure.[21,31–38,105,106] Human GRK4 65R>L and two other human GRK4 gene variants (GRK4 142A>V rs1024323, GRK4 486A>V rs1801058) constitutively impair dopamine receptor (types 1 and 3) function.[105] GRK4 gene variants cause hypertension in transgenic mice[105,106] and salt sensitivity (unpublished) and thus fulfill the essential test for the demonstration that these genetic variants are causal of a complex trait,[107] for example, hypertension and salt sensitivity.