# Microbiome, metabolites, and alcohol in HIV to reduce CVD Cohort (META HIV CVD Cohort)

> **NIH NIH P01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2024 · $503,806

## Abstract

Unhealthy alcohol use is common in people living with HIV (PLWH) and is associated with cardiovascular
disease (CVD) and mortality risk. Prior work suggests that heavy drinking alters gastrointestinal microbial
composition (i.e., gut dysbiosis) and gut dysbiosis may contribute to CVD risk. Gut dysbiosis impacts the
production of short chain fatty acids (SCFAs e.g., butyrate), bile acids (e.g., deoxycholic acid), and choline
metabolites (e.g., trimethylamine N-oxide, TMAO). Whether these microbiome-dependent metabolites are
associated with incident CVD and death and contribute to the excess risk of CVD among PLWH who are heavy
drinkers is unknown. Each of these three metabolic pathways (SCFA, bile acids, and choline), if associated
with CVD in PLWH, could serve as a potential therapeutic target to reduce CVD risk among PLWH who are
heavy drinkers. The central hypotheses in the Microbiome, Metabolites, and Alcohol in HIV to reduce CVD
(META HIV CVD) program project grant are that among PLWH, a probiotic can mitigate alcohol-associated
dysbiosis and reduce microbial translocation, inflammation and harmful microbiome-dependent metabolites
(Project 1); and that altered SCFA, bile acid and TMAO metabolism are associated with increased risk of CVD
and death (Project 2). Our preliminary data support the scientific premise that unhealthy alcohol use, gut
dysbiosis and resulting metabolite alterations contribute to gut permeability, immune dysfunction, CVD, and
death. META HIV CVD Cohort (Project 2), is a prospective, observational cohort study led by Dr. So-Armah
(Lead), Dr. Freiberg, and Dr. Barve. The study will use existing data and biospecimens from the Veterans
Aging Cohort Study (VACS). New data to be obtained include targeted metabolomics and updated adjudication
of major adverse cardiac events (myocardial infarction, ischemic stroke, coronary revascularization, heart
failure, peripheral artery disease). We will assess 3 microbiome-dependent metabolic pathways and determine
the association of metabolites from these pathways with alcohol, CVD, and death by HIV status. Aim 1
assesses SCFA metabolic pathways focusing primarily on butyrate, a metabolite necessary for intestinal cell
health. Aim 2 assesses choline metabolic pathways focusing primarily on trimethylamine N-oxide (TMAO), a
metabolite associated with increased CVD risk. Aim 3 assesses bile acid metabolic pathways focusing on the
deoxycholic acid to cholic acid ratio, which may be associated with dyslipidemia. For each aim, we will identify
metabolites independently associated with alcohol use, CVD, and/or death and determine whether these
associations are unique to or accentuated among PLWH vs. people without HIV. Aim 4 will replicate the
associations of heavy drinking and these metabolites with baseline data from the META HIV CVD clinical trial
participants (Project 1). IMPACT: This study advances understanding of how alcohol-associated gut dysbiosis
and dependent metabolites contribute to...

## Key facts

- **NIH application ID:** 10908497
- **Project number:** 5P01AA029542-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Kaku So-Armah
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $503,806
- **Award type:** 5
- **Project period:** 2021-09-10 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10908497

## Citation

> US National Institutes of Health, RePORTER application 10908497, Microbiome, metabolites, and alcohol in HIV to reduce CVD Cohort (META HIV CVD Cohort) (5P01AA029542-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10908497. Licensed CC0.

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