# Prenatal Opioid Exposure and Inflammation: The Role of the Microbiome and Epigenome.

> **NIH NIH F31** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $51,752

## Abstract

Project Summary
The heightened incidence of opioid use during pregnancy in the wake of the ongoing opioid crisis motivates this
targeted investigation into the impact of prenatal opioid exposure. Here, we examine the molecular mechanisms
through which prenatal opioid exposure produces systemic inflammation and immunosuppressive phenotypes
later in life. This result is consistent with systemic inflammatory response syndrome (SIRS) followed by the
corresponding compensatory anti-inflammatory response syndrome (CARS) that restricts harmful systemic
immune responses. Recent studies have implicated the role of microbial dysbiosis in systemic inflammation and
epigenetic modifications of macrophages in CARS-mediated immunosuppression. Specifically, adult models
have shown that following chronic opioid exposure, gut microbial dysbiosis initiates TLR4-induced systemic
inflammation. Opioid use during pregnancy results in gut dysbiosis that is strongly correlated with diversity and
taxonomy of the infant microbiome. Taken together, it is plausible that prenatal opioid exposure results in
neonatal gut microbial dysbiosis which contributes to systemic inflammation. Surprisingly, probiotic therapy does
not fully attenuate opioid-induced immune dysfunction, suggesting other mechanisms at play that contribute to
immunosuppressive phenotypes following SIRS such as epigenetic modifications of macrophages. H3K9me2
modifications in the IL-1β and TNFα promoters of macrophages following SIRS have commonly been described;
adult models of chronic opioid use have largely limited their analysis of these modifications to brain tissue where,
promisingly, differential expression of H3K9me2 modifications in several brain regions has been shown. Given
these preliminary findings, this project aims to study these modifications on a cellular level in intestinal
macrophages. I hypothesize that prenatal opioid exposure results in microbial dysbiosis, which
contributes to systemic inflammation; additionally, opioid-induced systemic inflammation that persists
postnatally alters the epigenome of intestinal macrophages which further perpetuates immune
dysfunction. To date, there have been no reported studies on how prenatal opioid exposure affects the gut
microbiome or how opioid-induced inflammation leads to epigenetic modifications of macrophages. Thus, the
goal of this project is to characterize immune dysfunction following prenatal opioid exposure and to define
underlying mechanisms through the following two Specific Aims. Aim 1. Determine how alterations in the gut
microbiome following prenatal opioid exposure contribute to systemic inflammation by examining gut microbial
and metabolome composition, gut barrier integrity, and TLR4-induced systemic inflammation. Aim 2.
Characterize immune dysfunction following prenatal opioid exposure and the effects of opioid-induced
inflammation on H3K9me2 modifications in intestinal macrophages. Collectively, this proposal will contribute an
in-...

## Key facts

- **NIH application ID:** 10235840
- **Project number:** 1F31DA053795-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Yaa Abu
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $51,752
- **Award type:** 1
- **Project period:** 2022-06-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10235840

## Citation

> US National Institutes of Health, RePORTER application 10235840, Prenatal Opioid Exposure and Inflammation: The Role of the Microbiome and Epigenome. (1F31DA053795-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10235840. Licensed CC0.

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