# Characterization of bacterial reductases acting on the A-ring of 11-oxy-androgens

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2022 · $35,873

## Abstract

Project Summary/Abstract
Literature from as early as 1957 from Nabarro et al demonstrated that glucocorticoids such as cortisol can be
converted into potent androgens like hydroxyandrostenedione (11β-OHAD) (1,2). However, it wasn't until 1981
that side-chain cleavage of cortisol was first observed in human stool suspensions (3). In 1984, researchers
isolated the human gut bacterium, Clostridium scindens, capable of steroid-17,20-desmolase (SD) (4,5). Ridlon
et al (2013) utilized RNA-Seq to identify the cortisol-inducible genes (desAB), which were later confirmed by our
laboratory to encode SD (6,7). The parent R01 seeks to study the contribution of both human gut bacteria
expressing DesAB as well as engineered E. coli expressing DesAB to circulating 11β-OHAD, and the effect of
this 11-oxy-androgen precursor on intestinal immune profile and gene expression. The aim of the proposed
diversity supplement is to extend the studies in the parent grant by characterizing human microbiome genes
encoding enzymes capable of further metabolism of 11β-OHAD into dihydro-stereoisomeric derivatives 11β-
OH-5α-dihydroandrostane (androgen-precursor) and 11β-OH-5β-dihydroandrostane (non-androgen precursor)
and integrating expression of these genes into gnotobiotic animal studies. These mechanistic studies represent
the first attempt to causally link gut microbial corticosteroid metabolism to circulating 11-oxy-androgen levels and
gastrointestinal function. This unique training opportunity integrates anaerobic bacteriology, microbial gene
discovery and enzyme characterization, CRISPR-Cas9 recombineering, gnotobiology, immunology, host and
microbial transcriptomics (RNA-Seq). Training will also consist of diverse career development and didactic
coursework including NUTR 550 Grant Writing Course (Ridlon co-instructor) and one-on-one grant and
manuscript writing development by the co-mentors, bioinformatics and statistical courses and HPCBio modules
on transcriptomic analysis, nutrition, microbial and mammalian biochemistry courses, and microbiology.

## Key facts

- **NIH application ID:** 10653436
- **Project number:** 3R01GM134423-03S1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Jason Michael Ridlon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $35,873
- **Award type:** 3
- **Project period:** 2020-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10653436

## Citation

> US National Institutes of Health, RePORTER application 10653436, Characterization of bacterial reductases acting on the A-ring of 11-oxy-androgens (3R01GM134423-03S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10653436. Licensed CC0.

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