# Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV

> **NIH NIH R01** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2022 · $44,265

## Abstract

Abstract
In the last decade the number of women with opioid use disorder at labor and delivery has more than
quadrupled. This translates to a rapid rise in the number of children and young adults with prenatal and early
postnatal history of opioid exposure. While it is known that chronic morphine use disrupts the gut microbiome
leading to impaired host immune response and increases inflammatory responses, the consequences of opioid
exposure in neonates and during nursing on opioid associated co-morbidities later in life are not known. Clinical
studies of opioid exposure in neonates and early childhood are complicated by mother-child interactions,
environmental stability, genetic variabilities and polysubstance use, lending animal models a more appropriate
tool to determine the long-term effects of opioid exposure in neonates and early childhood on subsequent
exposure to opioids later in life and its impact on opioid associated co-morbidities. Previous work from our lab
and our preliminary data show that morphine induces changes in the gut microbiome and metabolome. We
recently show that opioid induced microbial dysbiosis contributes to analgesictolerance and exacerbated
withdrawal behavior. These effects are attenuated in germ free miceand antibiotic induced microbial depleted
animals. The impact of maintenance opioids such methadone and buprenorphine on maternal microbial
dysbiosis and its consequence on fetal and post-natal gut brain axis development has not been
studied. Based on our lab's published findings, the central hypothesis of this proposal is that opioid exposure
during pregnancy and nursing will result in microbial dysbiosis in the mother leading to vertical transmission of
dysbiotic microbiome in off springs. Microbial dysbiosis in the off springs will leadto a dysregulated gut brain
axis contributing to opioid associated co-morbidities in adolescence and adulthood. The goal of this
supplement is to provide research training to the diversity candidate such that the candidate gains expertise in
several behavioral and biochemical techniques and concepts that links the gut microbiota to opioid associated
co-morbidities. The objective of the research proposal is to determine the long-term consequence of prenatal
and early postnatal exposure to morphine and maintenance opioids, Methadone and Buprenorphine on the gut
microbiome and its impact on behavioral outcomes and microglial inflammasome activation. AIM 1: We will
establish that neonates that are prenatally and postnatally exposed to morphine, methadone and
buprenorphine will have an altered a) gut microbiome and b) metabolome resulting in sustained
disruption in the gut brain axisthat persists through adolescence and adulthood. Aim 2: We will
establish that neonatesthat are prenatally and postnatally exposed to morphine, methadone and
buprenorphine induces microglial activation, inflammasome assembly and sustained inflammation
which lead to pain hypersensitization and contribute to ...

## Key facts

- **NIH application ID:** 10518777
- **Project number:** 3R01DA050542-04S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Sabita Roy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $44,265
- **Award type:** 3
- **Project period:** 2019-09-30 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518777

## Citation

> US National Institutes of Health, RePORTER application 10518777, Role of Gut Microbiome- Brain Axis in Modulating CNS Inflammasomes in the Neuropathology Produced by Opioid Exposure and HIV (3R01DA050542-04S1). Retrieved via AI Analytics 2026-06-02 from https://api.ai-analytics.org/grant/nih/10518777. Licensed CC0.

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