# The Impact of Perioperative Opioids on the Gut Estrobolome in Breast Cancer Patients

> **NIH NIH P30** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2023 · $191,875

## Abstract

Project Summary/Abstract
This application is being submitted in response to the Notice of Special Interest (NOSI) identified as NOT-CA-
21-100.
One in five opioid-naïve patients undergoing mastectomy is a persistent opioid user one year after surgery,
highlighting the burden of opioid use in women with breast cancer. Preclinical studies have shown that opioids
adversely impact the gut microbiome through bacterial translocation and the release of inflammatory cytokines,
which may influence secondary effects such as gastrointestinal disorders and even the progression of certain
cancers. The gut microbiome is also the site of steroid hormone metabolism. Specifically, bacteria of the distal gut
microbiome "reactivate” conjugated estrogens excreted into bile, allowing for re-entry into circulation. The
microbiome component responsible for liberating these biologically active estrogens is termed the “estrobolome.”
Increased estrogen metabolite concentration appears to be strongly associated with gut microbial diversity, and
a low ratio of estrogen metabolites to serum estradiol and estrone is associated with an increased risk of breast
cancer. Therefore, the estrobolome may influence the systemic concentration of sex steroids and oncologic
outcome. This proposal seeks to characterize the impact of perioperative opioids on the estrobolome and its
metabolites in a diverse cohort of women with breast cancer by comparing perioperative changes in the gut
microbiome between two groups of patients undergoing breast cancer surgery: those that receive standard
opioid-based pain management and those that receive a validated, opioid-sparing multimodal analgesia regimen.
Stool and blood samples will be collected before and one week after surgery to determine whether perioperative
opioid administration is associated with adverse changes in the gut microbiome. Specific microbial strains
associated with opioid-induced changes in the estrobolome will be stratified by antibiotic receipt (none, low, high)
to account for the potential influence of perioperative antibiotics. Aside from an additional impetus for other
surgeons to adopt similar opioid-sparing perioperative protocols, characterizing the impact of opioids on the gut
estrobolome in women with estrogen-sensitive breast cancer provides a novel and innovative method to inform
the development of future targets of intervention.

## Key facts

- **NIH application ID:** 10752298
- **Project number:** 3P30CA240139-05S1
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Stephen D. Nimer
- **Activity code:** P30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $191,875
- **Award type:** 3
- **Project period:** 2019-07-10 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10752298

## Citation

> US National Institutes of Health, RePORTER application 10752298, The Impact of Perioperative Opioids on the Gut Estrobolome in Breast Cancer Patients (3P30CA240139-05S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10752298. Licensed CC0.

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