Steroid biotransformations by host-associated bacteria

The National Institute of General Medical Sciences awarded the University of Illinois $453,722 on August 1, 2026, under the Biomedical Research and Research Training program (CFDA 93.859) to discover and characterize novel microbial enzymes capable of converting host steroids and steroid pharmaceuticals into androgen compounds.

The research focuses on steroid biotransformations by host-associated bacteria in human stool and urine samples. The investigator team will continue characterizing androgen-producing biochemical pathways and conduct basic discovery science using previously collected samples. The work builds on prior discoveries of desab genes encoding steroid-17,20-desmolase and subsequent identification of desf and desg genes that convert androstenedione to epitestosterone and testosterone, respectively, as well as novel steroid biotransformation pathways not previously reported in scientific literature.

The research seeks to identify microbial steroid biotransforming enzymes as novel therapeutic targets, recognizing that host-associated microbiota metabolize both endogenous steroids and steroid-based pharmaceuticals, contributing to inter-individual variation in drug efficacies through genetic and environmental factors.

Performance occurs in Urbana, Illinois, with a period of performance through April 30, 2031. This is a Project Grant assistance type award.

Abstract

Steroid hormones play essential roles in the regulation of water and salt balance, stress response, immune regulation, cholesterol homeostasis and digestion, energy and lipid homeostasis, glucose and insulin homeostasis, microbiome structure and function, initiation and regulation of sexual differentiation and reproduction, and malignancy. A significant section of any pharmacopeia is replete with steroidogenic drugs from altocor and arimidex to zocor and zytiga. Yet the efficacies of these therapies vary between individuals through an interplay of genetic and environmental factors. Indeed, microbiota that colonize the human body are an environmental factor with a genetic component that (1) metabolize host steroids, and (2) metabolize pharmaceuticals. The microbial steroid biotransforming enzymes may therefore represent novel therapeutic targets. The focus of this R35 is to discover and characterize novel microbial enzymes in human stool and urine capable of converting host steroids and steroid pharmaceuticals into androgen compounds. We previously discovered and characterized the desab genes encoding steroid-17,20-desmolase involved in side-chain cleavage of cortisol to androgen precursors. During GM145920 funding, we discovered desf and desg, which convert androstenedione to epitestosterone and testosterone, respectively. We also discovered novel steroid biotransformation pathways that have not been previously reported. We propose to continue characterizing these novel androgen-producing biochemical pathways, and continue basic discovery science with already collected urine and fecal samples.