The Gut Microbiome, Inflammation, and Salt-Sensitive Hypertension

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 salt-induced 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. 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: Immune activation; Microbiome; Salt-sensitive hypertension.

Fig. 1

Hypothesized model of how the gut microbiome may contribute to inflammation and salt-sensitive hypertension. Excess dietary salt alters the gut microbiome and activates DCs to produce ROS via NADPH oxidase. ROS production leads to IsoLG-adducted protein formation, presentation of co-stimulatory factor CD86, and secretion of pro-inflammatory factors IL-6 and IL-1β. The activated DCs promote T cell activation and stimulate the release of IL-17, TNF-α𝑎, and IFN-γ, leading to hypertension