# Microbiome, Metabolites, and Alcohol in HIV to Reduce CVD (META HIV CVD)

> **NIH NIH P01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $1,774,823

## Abstract

The overarching theme for this program project grant (PPG) is that alcohol associated gut dysbiosis and gut
dysbiotic metabolites are cardiovascular disease (CVD) risk factors among people living with HIV infection
(PLWH) who are heavy drinkers. The goals of this research are (1) to determine if a tailored probiotic (i.e.,
contains bacteria supporting butyrate synthesis) can mitigate alcohol associated gut dysbiosis and lower levels
of microbial translocation, inflammation, and improve harmful dysbiotic metabolite profiles (e.g. trimethylamine
N oxide, TMAO) and (2) to determine if these metabolites are associated with incident CVD and death among
PLWH. We hypothesize that, among PLWH, a probiotic vs. placebo can mitigate alcohol associated gut
dysbiosis and lower levels of microbial translocation, inflammation, and improve metabolite profiles (Project 1
RCT, n=250); and that harmful alterations of these metabolites will be associated with higher risk of incident
CVD and death (Project 2 Cohort, n=2,900). Project 1 will be conducted at Pavlov State Medical University in
St. Petersburg, Russia, the same site as our gut microbiome and metabolite studies (ACME HIV and TMAO
HIV). Project 2 will leverage the Veterans Aging Cohort Study, an observational cohort of veterans living with
and without HIV. The Projects will be supported by our Administrative Core at Vanderbilt University Medical
Center and the Integrated Metagenomics and Metabolomics Core at the University of Louisville's Alcohol
Research Center (ULARC). The latter is the core for ACME HIV and will generate the metagenomics and
metabolomics for this PPG. The former will coordinate all study projects/cores and integrate the Vanderbilt
SCHolars in HIV and Heart, Lung, Blood, and Sleep ReSearch NIH K12 training program into the PPG. Our
preliminary data: (1) HIV infection is a CVD risk factor; (2) inflammation is associated with increased risk of
CVD among PLWH; (3) among PLWH, heavy drinking is associated with increased CVD risk and correlated
with measures of gut dysbiosis, characterized by loss of butyrate producing bacteria; (4) gut dysbiosis among
PLWH who are heavy drinkers is correlated with higher levels of inflammation, TMAO, and adverse bile acid
metabolite profiles; and (5) ULARC data in murine models show heavy drinking causes dysbiosis, that
dysbiosis leads to increased biomarker levels of inflammation, and that probiotic administration targeting
alcohol-associated gut dysbiosis attenuates the rise in these inflammatory biomarkers even in the presence of
alcohol consumption. Cross project validation: Biospecimens from Project 1 will be used to validate
significant findings in Project 2. Metabolites significantly associated with alcohol and CVD in Project 2, will be
explored in Project 1 to see if probiotics favorably impact the levels of those metabolites. The Microbiome,
METabolites, and Alcohol in HIV to reduce CVD (META HIV CVD) PPG will inform probiotics' role as standard
adju...

## Key facts

- **NIH application ID:** 10908485
- **Project number:** 5P01AA029542-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** SHIRISH S BARVE
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $1,774,823
- **Award type:** 5
- **Project period:** 2021-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908485

## Citation

> US National Institutes of Health, RePORTER application 10908485, Microbiome, Metabolites, and Alcohol in HIV to Reduce CVD (META HIV CVD) (5P01AA029542-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908485. Licensed CC0.

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