# Alcohol assoCiated gut Dysbiosis and CVD in HIV (the AC/DC HIV study)

> **NIH NIH R01** · BROWN UNIVERSITY · 2024 · $698,356

## Abstract

PROJECT ABSTRACT: Among people with HIV infection (PWH), hazardous drinking is a common, modifiable
risk factor for cardiovascular disease (CVD) and death. Both alcohol and HIV cause gut dysbiosis. Gut
dysbiosis is associated with systemic inflammation and harmful metabolites, each of which is associated with
CVD and death. However, the specific bacterial shifts that drive dysbiosis and its harmful effects among PWH
who drink are unclear. Our overarching model posits that alcohol associated gut dysbiosis leads to a
reduction in specific species of butyrate-producing bacteria, lowering butyrate levels and increasing
trimethylamine N-oxide (TMAO). These mechanisms contribute to microbial translocation and vascular
inflammation. Ultimately, these processes promote CVD and excess mortality. This application leverages rich
existing data from three fully harmonized NIAAA cohort studies (ACME HIV, U01AA026222; TMAO HIV,
R01AA025859; META HIV, P01AA029542) in response to NOT-AA-23-011 requesting proposals for use of
existing data and biospecimens in alcohol research. We hypothesize that alcohol associated gut dysbiosis will
be characterized by reductions in butyrate-producing species (Aim 1); that reductions in these species will
associate with increased levels of microbial translocation, inflammation, and harmful metabolites (Aim 2); and
that reductions in butyrate-producing species will associate with greater subclinical CVD dysfunction, CVD risk,
and mortality risk (Aim 3). Prior studies examining alcohol associated dysbiosis in PWH are limited in
two major ways: (1) they rely on 16S characterization of the gut microbiome, which cannot provide granular
(i.e., species level) data; or (2) they employ whole genome sequencing (WGS) to collect species level data, but
only in small samples. Our application is innovative because it addresses both limitations by utilizing WGS in
three existing, fully harmonized NIAAA-funded studies involving 583 PWH who consume alcohol with >1700
longitudinal fecal specimens. Extant data include alcohol measures (AUDIT; Timeline Followback, TLFB;
phosphatidyl ethanol, PEth), stored serum/plasma and fecal samples, 16S gut microbiome data, and serum
biomarkers for metabolites (e.g., TMAO), microbial translocation (e.g., LBP), inflammation (e.g., IL-6), VACS
Index (mortality) and Reynolds Risk (CVD) scores, and echocardiograms. New data to be generated are
WGS on all fecal samples from the three studies. Specific Aims are as follows: Aim 1: To characterize
alcohol associated dysbiosis using WGS, employing longitudinal fecal specimens. Aim 2: To test the relations
of the gut microbiome at species/strain-level with markers of microbial translocation, inflammation, and harmful
metabolites. Aim 3: To test the association of species/strain-level changes in butyrate-producing and other gut
bacteria with subclinical CVD markers, CVD risk, and mortality risk. IMPACT: Precision medicine approaches
utilizing gut microbiota profiles at the...

## Key facts

- **NIH application ID:** 11085700
- **Project number:** 1R01AA031640-01A1
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Mollie A Monnig
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $698,356
- **Award type:** 1
- **Project period:** 2024-09-25 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11085700

## Citation

> US National Institutes of Health, RePORTER application 11085700, Alcohol assoCiated gut Dysbiosis and CVD in HIV (the AC/DC HIV study) (1R01AA031640-01A1). Retrieved via AI Analytics 2026-06-25 from https://api.ai-analytics.org/grant/nih/11085700. Licensed CC0.

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