# Gut Microbiota and Cerebral Vascular Disease

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2021 · $551,373

## Abstract

Project Summary:
Cerebral vascular disease is one of the leading causes of mortality and disability worldwide. Ischemic stroke,
accounting for the majority of all strokes, occurs when a blood clot blocks regional cerebral blood flow. The
precipitating pathophysiological process for this catastrophic event is often platelet hyperreactivity, heightening
thrombosis potential. Enhanced platelet reactivity increases the susceptibility for acute thrombotic occlusion of
vessels, such as during ischemic stroke and heart attack. Over the past few years, we have developed
mechanistic links between nutrients in a Western diet, gut microbiota formation of the metabolite trimethylamine
N oxide (TMAO), and development of both platelet hyper-responsiveness and cardiovascular diseases. In
exciting new unpublished studies, we have obtained substantial evidence indicating that the gut microbial TMAO
pathway can directly contribute to the development and severity of ischemic stroke and its downstream adverse
outcomes. Our proposal aims to confirm and test the hypothesis that gut microbiota, through the metaorganismal
(involving both microbes and host) TMAO pathway, contributes to stroke risks. We will evaluate the role of this
pathway in enhancing stroke risks by impacting platelet function, fostering worse functional impairment by
augmenting cerebral inflammation via NLRP3 inflammasome activation in brain tissue. We will also examine the
role of gut microbes in modulating stroke susceptibility and functional recovery post stroke onset, identify
potential mechanisms contributing diet enhanced ischemic stroke risks, and explore novel therapeutic
approaches targeting gut microbial contributions for prevention and treatment in cerebrovascular disease.
Completion of the proposed studies will not only provide proof of concept, but also provide preclinical evidence
that drugging the microbiome may serve as a novel strategy to prevent and treat cerebrovascular diseases.

## Key facts

- **NIH application ID:** 10197216
- **Project number:** 5R01HL150537-02
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Weifei Zhu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $551,373
- **Award type:** 5
- **Project period:** 2020-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197216

## Citation

> US National Institutes of Health, RePORTER application 10197216, Gut Microbiota and Cerebral Vascular Disease (5R01HL150537-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10197216. Licensed CC0.

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