The Gut Microbiome, Inflammation, and Salt-Sensitive Hypertension
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GUT MICROBIOME AND HYPERTENSION (J FERGUSON, SECTION EDITOR)
The Gut Microbiome, Inflammation, and Salt-Sensitive Hypertension Fernando Elijovich 1 & Cheryl L. Laffer 1 & Melis Sahinoz 2 & Ashley Pitzer 1 & Jane F. Ferguson 3 & Annet Kirabo 1,4
# The Author(s) 2020
Abstract Purpose of Review Salt sensitivity of blood pressure (SSBP) is an independent predictor of death due to cardiovascular events and affects nearly 50% of the hypertensive and 25% of the normotensive population. Strong evidence indicates that reducing sodium (Na+) intake decreases blood pressure (BP) and cardiovascular events. The precise mechanisms of how dietary Na+ contributes to elevation and cardiovascular disease remain unclear. The goal of this review is to discuss mechanisms of saltinduced cardiovascular disease and how the microbiome may play a role. Recent Findings The innate and adaptive immune systems are involved in the genesis of salt-induced hypertension. Mice fed a high-salt diet exhibit increased inflammation with a marked increase in dendritic cell (DC) production of interleukin (IL)-6 and formation of isolevuglandins (IsoLG)-protein adducts, which drive interferon-gamma (IFN-γ) and IL-17A production by T cells. While prior studies have mainly focused on the brain, kidney, and vasculature as playing a role in salt-induced hypertension, the gut is the first and largest location for Na+ absorption. Research from our group and others strongly suggests that the gut microbiome contributes to salt-induced inflammation and hypertension. Summary Recent studies suggest that alterations in the gut microbiome contribute to salt-induced hypertension. However, the contribution of the microbiome to SSBP and its underlying mechanisms are not known. Targeting the microbiota and the associated immune cell activation could conceivably provide the much-needed therapy for SSBP. Keywords Salt-sensitive hypertension . Microbiome . Immune activation
Introduction Hypertension is a growing health care burden and is the leading cause of mortality due to myocardial infarction, stroke, heart failure, and chronic kidney disease. Recently, the This article is part of the Topical Collection on Gut Microbiome and Hypertension * Annet Kirabo [email protected] 1
Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Room 536 Robinson Research Building, Nashville, TN 37232-6602, USA
2
Department of Medicine, Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN, USA
3
Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, TN, USA
4
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN, USA
American Heart Association (AHA) and the American College of Cardiology (ACC) developed new classification criteria that put nearly half of the American US population in the hypertensive category [1]. Accordingly, the
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