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Peer-reviewedCC BYFrontiers in medicine

The gut-brain-vascular axis: converging neuroinflammatory and hypertension-mediated pathways from gut dysbiosis to cognitive decline

  • Shaurya Mehta1
  • Pranav Loomba2
  • Hamoudi Musselmani3
  • Jaret Ly1
  • Sami Nguyen3
  • Alex Niemann3
  • Sree Kolli4
  • David Sant3
4 affiliations
  1. 1University of Utah Health , , ,
  2. 2California University of Science and Medicine , , ,
  3. 3Department of Biomedical Sciences, Noorda College of Osteopathic Medicine , , ,
  4. 4Saint Louis University School of Medicine , , ,
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Abstract

Hypertension and cognitive decline are major public health burdens, and both have been associated with gut microbiome dysbiosis. We propose the gut-brain-vascular axis as a testable synthesis in which dysbiosis may contribute to cognitive decline through two converging routes: direct neuroinflammatory signaling and hypertension-mediated cerebrovascular injury. In the proposed direct route, intestinal barrier dysfunction, lipopolysaccharide translocation, altered microbial metabolites, microglial activation, and vagal signaling may promote neuroinflammation. In the indirect route, dysbiosis-associated metabolites, immune activation, autonomic imbalance, and endothelial injury may contribute to hypertension, which is linked to cerebral small vessel disease, impaired cerebral autoregulation, neurovascular uncoupling, and blood-brain barrier dysfunction. The component relationships are supported to different degrees, but the complete temporal pathway and an interaction between the two routes have not been established in humans. This narrative review synthesizes gut-hypertension, gut-cognitive, cerebrovascular, shared-mechanism, and therapeutic evidence and identifies the study designs needed to test the framework. Longitudinal cohorts and trials that measure microbiome, blood pressure, cerebrovascular, and cognitive outcomes together are required to determine whether the proposed routes occur independently, sequentially, or interactively.

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Cite

BibTeXRIS
BibTeX
@article{mehta2026gutbrainvascular,
  title = {{The gut-brain-vascular axis: converging neuroinflammatory and hypertension-mediated pathways from gut dysbiosis to cognitive decline}},
  author = {Shaurya Mehta and Pranav Loomba and Hamoudi Musselmani and Jaret Ly and Sami Nguyen and Alex Niemann and Sree Kolli and David Sant},
  journal = {Frontiers in medicine},
  year = {2026},
  month = oct,
  doi = {10.3389/fmed.2026.1928026},
  url = {https://europepmc.org/article/PMC/PMC13725819},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - The gut-brain-vascular axis: converging neuroinflammatory and hypertension-mediated pathways from gut dysbiosis to cognitive decline
AU  - Shaurya Mehta
AU  - Pranav Loomba
AU  - Hamoudi Musselmani
AU  - Jaret Ly
AU  - Sami Nguyen
AU  - Alex Niemann
AU  - Sree Kolli
AU  - David Sant
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in medicine
DO  - 10.3389/fmed.2026.1928026
UR  - https://europepmc.org/article/PMC/PMC13725819
AB  - Hypertension and cognitive decline are major public health burdens, and both have been associated with gut microbiome dysbiosis. We propose the gut-brain-vascular axis as a testable synthesis in which dysbiosis may contribute to cognitive decline through two converging routes: direct neuroinflammatory signaling and hypertension-mediated cerebrovascular injury. In the proposed direct route, intestinal barrier dysfunction, lipopolysaccharide translocation, altered microbial metabolites, microglial activation, and vagal signaling may promote neuroinflammation. In the indirect route, dysbiosis-associated metabolites, immune activation, autonomic imbalance, and endothelial injury may contribute to hypertension, which is linked to cerebral small vessel disease, impaired cerebral autoregulation, neurovascular uncoupling, and blood-brain barrier dysfunction. The component relationships are supported to different degrees, but the complete temporal pathway and an interaction between the two routes have not been established in humans. This narrative review synthesizes gut-hypertension, gut-cognitive, cerebrovascular, shared-mechanism, and therapeutic evidence and identifies the study designs needed to test the framework. Longitudinal cohorts and trials that measure microbiome, blood pressure, cerebrovascular, and cognitive outcomes together are required to determine whether the proposed routes occur independently, sequentially, or interactively.
SN  - 2296-858X
ER  -