# Role of Microbial dysbiosis and altered metabolomics in the context of Opioid abuse and ART in HIV disease progression

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2020 · $622,803

## Abstract

Abstract/Project Summary
Gut leakiness, microbial translocation and systemic inflammation are hallmarks of HIV disease progression.
Interestingly, chronic opioid abuse is also well documented to induce gut leakiness and sustained systemic
inflammation. HIV patients that use intravenous heroin display accelerated HIV disease progression. Although
HIV replication is suppressed in HIV-infected adults on modern ART regimens microbial translocation
continues long after peripheral CD4+ T cell restoration. The resulting activation of both the innate and adaptive
immune systems in ART treated HIV individuals is reported to be associated with markers of inflammation and
is an independent predictor of morbidity and mortality. The role of ART in driving the inflammatory process has
not been documented. Thus far, very little is known regarding the underlying mechanisms that contribute to
gut leakiness and microbial translocation in either opioid abusers or in HIV patients that are on ART.
Increasing number of studies strongly support the concept that the gut microbiota, play a significant role in
maintaining gut homeostasis and gut barrier function. Under both homeostatic and disease conditions the
microbiota influences immune function in several ways, including the release of metabolites and direct
microbial interactions. Although a few studies have correlated the host microbiome in HIV infected patients with
the metabolome, the interaction between the ``omics'' level analysis and the gut barrier function in the context
of antiretroviral treatment (ART) still remain largely unexplored. There is no data on the interaction of the
microbiome-metabolome-gut barrier in HIV patients in the context of opioid abuse. The goal of this study is to
develop an integrated pipeline for identifying novel connections between the microbiome-metabolome and gut
barrier function following HIV infection and HIV infection in the context of Drug Abuse. We will further
investigate if treatment with ART restores homeostasis or exacerbates dysbiosis.
Specific Aim 1: a) Identification of unique biomarkers and signature profiles in the gut microbiome that are
associated with HIV disease progression in the context of opioid abuse and ART b) Determine if altered
signature profiles is associated with metabolic consequences and immune activation.
Specific Aim 2. Establish a causal relationship between gut dysbiosis, altered metabolome and barrier
disruption following HIV infection and in the context of opioid drug abuse and ART using germ free and
antibiotic treated humanized mice.
Specific Aim 3. Establish that Probiotics will restore gut homeostasis and delay HIV disease progression in
the context of opioid abuse and ART.
The results from these studies will allow for the development of a pipeline for new therapeutic strategies to
attenuate immune activation and reverse HIV disease progression both in HIV infected patients and in HIV
infected drug abusing population.

## Key facts

- **NIH application ID:** 9850949
- **Project number:** 5R01DA043252-04
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sabita Roy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $622,803
- **Award type:** 5
- **Project period:** 2017-03-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9850949

## Citation

> US National Institutes of Health, RePORTER application 9850949, Role of Microbial dysbiosis and altered metabolomics in the context of Opioid abuse and ART in HIV disease progression (5R01DA043252-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9850949. Licensed CC0.

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