REVIEW article
Front. Physiol.
Sec. Renal Physiology and Pathophysiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1653387
This article is part of the Research TopicThe Role of the Nervous System in the Pathophysiology of Hypertension and Kidney DiseaseView all articles
The Immune-Microbiome Axis in Salt-Sensitive Hypertension: A Focus on Renal and Neural Mechanisms
Provisionally accepted
- 1Universidade Federal de Ouro Preto, Ouro Preto, Brazil
- 2Emory University, Atlanta, United States
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Systemic arterial hypertension (SAH) is a prevalent condition affecting humans and other mammals, with high salt intake recognized as a major risk factor for its development and progression. This review examines the intricate interplay between dietary salt, immune signaling, neural regulation and renal mechanisms in the pathophysiology of salt-sensitive hypertension (SSH). High salt consumption not only directly influences blood pressure but also induces low-grade inflammation by activating both innate and adaptive immune responses, particularly promoting pro-inflammatory T cell (TH17/IL-17) and macrophage phenotypes. These immune alterations impact key organs involved in blood pressure regulation, including the kidneys and central nervous system (CNS). In the CNS, salt-induced immune activation, especially microglial activation and cytokine production in regions such as the paraventricular nucleus, enhances sympathetic outflow and contributes to neurogenic hypertension. Disruption of the blood-brain barrier further facilitates immune cell infiltration and perpetuates neuroinflammation. Additionally, recent evidence shows that high salt intake alters the gut microbiome, reducing its diversity and favoring pro-inflammatory bacterial populations, which further amplify immune dysregulation via the gut-grain axis. The role of the kidneys in sodium handling is modulated by immune cell infiltration and cytokine-drive changes in sodium channel expression, reinforcing salt sensitivity. Aging and sex differences further modulate these pathways, increasing SSH risk in older individuals and postmenopausal women. Emerging therapeutic strategies targeting the gut microbiota, immune signaling, and neural pathways offer promise improvement for SAH management. However, further research is needed to clarify causal mechanisms and optimize interventions that address the neural-immune-microbiome axis in hypertension.
Keywords: Hypertension, salt, Inflammation, microbiome, Short Chain Fatty Acids, Brain, Kidney, Salt sensitivity
Received: 24 Jun 2025; Accepted: 28 Aug 2025.
Copyright: © 2025 Cardoso and Wainford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Richard Wainford, Emory University, Atlanta, United States
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