# Gut Microbiome and Steroid Hormones

> **NIH NIH R21** · RUSH UNIVERSITY MEDICAL CENTER · 2020 · $204,533

## Abstract

ABSTRACT
GI tract microbiome is highly metabolically active, comparable to the host's liver. It has a significant role in the
bioavailability and the physiological effects of chemicals within foods and medications, esp. those that undergo
enterohepatic circulation (with excretion from the liver into the bile and the reabsorption back from the
intestines). One group of chemicals that are extensively metabolized in the GI tract and/or undergo
enterohepatic circulation are steroid hormones (such as estrogens, progestogens, androgens). The overall
goal of this translational R21 proposal is to identify bacterial taxa and their candidate genes that
contribute to the metabolism of steroid hormones within the GI tract. Thereby, this proposal lays the
groundwork for individualized microbiome-based precision medicine therapies that can target steroid
hormone metabolism in the GI tract. One specific example in which steroid hormones are related to a
disease is breast cancer (BC): Exposure to high levels of estrogens is a well-known risk factor for BC.
Although many hypotheses have been put forth that the GI tract microbiota play a role in BC primarily in terms
of the enterohepatic circulation of estrogens, alterations in bacterial taxa in BC are not known. We undertook
the first study to look at bacterial taxa in the gut mucosa of breast cancer patients and our data support our
model for a role for bacterial taxa in breast cancer. We also identified two novel associations between steroid
hormones and bacterial genera. This preliminary data suggests that a person's own gut microbiota may
contribute to the development of BC by directly affecting the availability of steroid hormones.
Importantly however, the majority of the bacterial taxa and their genes responsible for steroid hormone
metabolism in the gut are still unknown. We hypothesize that the GI tract microbiome is different in BC; and
that there are GI tract bacteria and their genes/proteins that are yet to be identified that directly metabolize
steroid hormones. Hence, we propose the following Specific Aims: Aim 1. Characterize fecal bacterial taxa
and steroid hormone levels in BC patients and controls with metagenomic sequencing and also with a
second sample set. Aim 2. Identify bacterial taxa and their candidate genes that metabolize steroid
hormones. We will perform metagenomics sequencing in patient and control samples. We will also determine
the ability of whole bacterial communities from feces of BC patients and controls and two specific bacterial taxa
in metabolizing steroid hormones. Sample will be examined with 16S rDNA sequencing, shot-gun
metagenomics and metatranscriptomics to identify bacterial communities and their metabolic genes that are
enhanced with steroid hormone exposure. Understanding which bacterial taxa may play a role in the
metabolism of steroid hormones in the GI tract and identification of bacterial taxa and genes that are involved
in steroid metabolism can potentially be u...

## Key facts

- **NIH application ID:** 10054472
- **Project number:** 1R21TR003105-01A1
- **Recipient organization:** RUSH UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Serdar E. Bulun
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $204,533
- **Award type:** 1
- **Project period:** 2020-08-11 → 2022-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10054472

## Citation

> US National Institutes of Health, RePORTER application 10054472, Gut Microbiome and Steroid Hormones (1R21TR003105-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10054472. Licensed CC0.

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