Abstract and Introduction
Purpose of review Hypertension, which is present in about one quarter of the world's population, is responsible for about 41% of the number one cause of death – cardiovascular disease. Not included in these statistics is the effect of sodium intake on blood pressure, even though an increase or a marked decrease in sodium intake can increase blood pressure. This review deals with the interaction of gut microbiota and the kidney with genetics and epigenetics in the regulation of blood pressure and salt sensitivity.
Recent findings The abundance of the gut microbes, Firmicutes and Bacteroidetes, is associated with increased blood pressure in several models of hypertension, including the spontaneously hypertensive and Dahl salt-sensitive rats. Decreasing gut microbiota by antibiotics can increase or decrease blood pressure that is influenced by genotype. The biological function of probiotics may also be a consequence of epigenetic modification, related, in part, to microRNA. Products of the fermentation of nutrients by gut microbiota can influence blood pressure by regulating expenditure of energy, intestinal metabolism of catecholamines, and gastrointestinal and renal ion transport, and thus, salt sensitivity.
Summary The beneficial or deleterious effect of gut microbiota on blood pressure is a consequence of several variables, including genetics, epigenetics, lifestyle, and intake of antibiotics. These variables may influence the ultimate level of blood pressure and control of hypertension.
Blood pressure is distributed continuously from low to high values, but the distribution is skewed to the higher end of the curve. There is a direct and quantitative relationship between high blood pressure values and mortality. Hypertension is a major contributor to the number one cause of death – cardiovascular disease. The Gaussian distribution and the lack of a definable bimodal distribution of blood pressure suggest that blood pressure is regulated by a complex group of interacting genes. The variation of blood pressure is further influenced by the interaction of these genes with epigenetic and environmental factors.[3–8] This review deals with the interaction of gut microbiota with genetics and epigenetics in the regulation of blood pressure and salt sensitivity.
Salt sensitivity, defined as more than 5–10% change in blood pressure in response to a change in NaCl intake, is associated with increased cardiovascular risk, even if the blood pressure does not reach hypertensive levels. Mortality and morbidity are both higher in hypertensive as well as in salt-sensitive normotensive patients, than in salt-resistant normotensive patients.[10–12] About 118 million Americans are afflicted with hypertension or salt sensitivity. Fifty to 60 million (≥18 years old) are hypertensive and 58 million are salt-sensitive; 26 million are both salt-sensitive and hypertensive.[10,13] It is recognized that a high sodium diet is deleterious and a low sodium diet has been advocated as part of a healthy life style and treatment of hypertension.[2,12] However, low sodium diet can actually increase blood pressure, that is, inverse salt sensitivity,[13–15] with other adverse consequences.[16–18] The mechanisms leading to such adverse consequences and their relationship to 'salt-resistant' and 'salt-sensitive' genes are not known.
The long-term regulation of blood pressure rests on renal and nonrenal mechanisms.[19–21] The impaired renal sodium handling in essential hypertension and salt sensitivity are caused by aberrant counter-regulatory natriuretic and antinatriuretic pathways. The nervous system, including renal nerves[22–25] and the parasympathetic and sympathetic nervous systems, renin–angiotensin–aldosterone system,[24,25,27–29] and endothelin via the endothelin type A receptor are examples of antinatriuretic pathways. An important counter-regulatory natriuretic pathway is afforded by the renal dopaminergic system. Aberrations of this system are involved in the pathogenesis of hypertension,[26,31–35] including that associated with obesity.[36–38] However, the gastrointestinal tract has to be integrated in the overall regulation sodium balance and blood pressure because it is the first organ exposed to ingested sodium.[39,40] Inhibition of gastrointestinal sodium transport is now being considered in the treatment of essential hypertension. Moreover, the gut microbiota can modify the expression of the hypertensive phenotype.[42–44]
Curr Opin Nephrol Hypertens. 2015;24(5):403-409. © 2015 Lippincott Williams & Wilkins