# Elucidating the role of the gut metagenome in hypertension.

> **NIH NIH F31** · MEDICAL COLLEGE OF WISCONSIN · 2021 · $46,036

## Abstract

Project Summary
Cardiovascular disease (CVD) is the leading cause of death world-wide. The primary modifiable risk factor for
CVD is hypertension (HTN), which is exacerbated by high sodium intake. One third of Americans are
hypertensive, of which half exhibit salt-sensitive HTN. Additionally, 12% of HTN patients do not respond to
treatment using standard medications. Taken together, these statistics highlight the critical need to elucidate the
mechanisms involved in the development of HTN for the design of alternative treatment options. The gut
microbiome has been implicated in many diseases including HTN. This project is designed to identify HTN-
exacerbating or protective bacteria and their associated metabolic genes to inform the design of
microbiome-based therapeutics for the treatment of HTN. Our preliminary results demonstrate that severe
HTN induced by salt consumption correlates with shifts in the gut microbial community of Dahl salt-sensitive (SS)
rats. Therefore, we tested the potential for the gut microbiota to affect HTN by performing a fecal material transfer
(FMT) from hypertensive Dahl SS into HTN-resistant rats. We demonstrated that the microbiome was sufficient
to exacerbate HTN in recipients and corresponded with statistically significant shifts in the gut microbiome. These
results lead us to hypothesize that the gut microbiota directly influences HTN.
Aim 1 will evaluate the role of bacterial supplementation during onset of HTN in the Dahl SS rat model.
Predetermined strains identified from our preliminary experiments will be grown in vitro and transferred into SS
Dahl rats and the effect on blood pressure and kidney damage will be evaluated. Potential mechanisms through
which the bacteria influence the severity of HTN will be explored by measuring metabolite production, evaluating
gut barrier function, and identifying shifts in the gut microbiome. Aim 2 will utilize machine learning to identify
specific gut bacteria and metabolic genes that serve as signatures for the severity of HTN. Experiments
in this aim will exploit shotgun metagenomic sequencing and computational approaches to identify specific
bacteria and metabolic genes associated with HTN. Their use as predictive biomarkers for HTN will be validated
by PCR-based analysis.
This work will take place in the laboratory of Dr. John Kirby in the Department of Microbiology & Immunology
(M&I) at the Medical College of Wisconsin, a highly collaborative and stimulating environment that is well
equipped to perform the proposed aims. The Department of M&I offers a state-of-the-art educational program
and various opportunities to explore alternative career pathways. We have designed a complementary training
plan for my scientific and professional growth that will position me to reach my goal of becoming an independent
biomedical scientist. In all, this project is critical for my advancement as a Latina woman in biomedical research,
the field of HTN research, and the generation of...

## Key facts

- **NIH application ID:** 10271244
- **Project number:** 5F31HL152495-02
- **Recipient organization:** MEDICAL COLLEGE OF WISCONSIN
- **Principal Investigator:** Fatima L Saravia
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 5
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271244

## Citation

> US National Institutes of Health, RePORTER application 10271244, Elucidating the role of the gut metagenome in hypertension. (5F31HL152495-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10271244. Licensed CC0.

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