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Bacteria in the urinary tract can convert corticosteroids into androgens, hormones that promote the growth of prostate cancer, according to research findings.

Researchers have discovered that bacteria in the urinary tract can convert corticosteroids into androgens, hormones that promote the growth of prostate cancer, substantially broadening current concepts of microbe-host endocrine crosstalk, according to findings published in Nature Microbiology.

“Commensal bacteria have been implicated in the modulation of steroid hormones, including circulating androgen levels in the host,” wrote study author Jason M. Ridlon, PhD, of the University of Illinois Urbana-Champaign, and colleagues. “However, the microbial genetic pathways involved in androgen production have not been fully characterized.”

Bacterial Bypass

Through comparative genomics, biochemical reconstitution, and androgen-responsive reporter assays, the authors discovered desF, a gene in Clostridium scindens encoding an enzyme that converts androsterone, an adrenal-derived precursor, into epitestosterone. The team demonstrated that the resultant bacterial metabolite promoted androgen receptor–dependent proliferation of prostate cancer cells in vitro.

The researchers also observed elevated stool levels of the desF gene in patients with prostate cancer unresponsive to standard abiraterone and prednisone therapy.

Microbial Resistance to Endocrine Therapy

According to the authors, abiraterone blocks the human enzyme CYP17A1, a key catalyst in adrenal steroidogenesis; however, bacterial enzymes, such as desF and the microbiota-encoded desmolase complex DesAB, are unaffected by this pharmacological blockade. These microbial pathways therefore supply a parallel source of receptor-activating androgens, offering a cogent explanation for persistent tumor growth in some patients who appear hormonally suppressed according to conventional serum assays, they explained.

Clinical Implications of Androgen-Producing Commensals

Furthermore, the research team identified bacteria from urinary and prostatectomy tissue capable of producing androgens, specifically Propionimicrobium lymphophilum, a urinary tract commensal. This organism carries the desG gene encoding 7β-hydroxysteroid dehydrogenase activity, a necessary enzyme in steroid metabolism. The authors mentioned that the presence in urinary strains suggests that P. lymphophilum produces androgens that promote the growth of prostate cancer cells by utilizing both natural (eg, cortisol) and therapeutic (eg, prednisone) glucocorticoid sources. They noted that prior studies have shown that the prevalence P lymphophilum in urine is linked to prostate cancer.

An Expanding Research Frontier

“We speculate that long-term colonization of the urinary tract by androgen-producing bacteria may be an underrecognized promoter of the development and/or progression of prostate cancer in some individuals,” concluded the researchers. “Further clinical and mechanistic microbiome studies examining the role of androgen-producing bacteria in the urinary tract in primary prostate cancer is warranted.”

Future therapeutic directions may therefore encompass microbiome-targeted antibiotics, precision probiotics, or enzyme-specific inhibitors designed to disarm these newly discovered microbial steroidogenic pathways.