Bacteria That Make Testosterone Could Undermine Prostate Cancer Drugs

Prostate cancer treatment has one reliable failure point: hormone-blocking drugs work, until they don't. Doctors have long suspected that resistance sometimes comes from androgens (testosterone-family hormones) the drugs simply cannot reach, and a study published in April 2025 in Nature Microbiology now points to one place at least some of that hidden hormone supply could be coming from: bacteria living in the human gut and urinary tract that carry their own genetic machinery for manufacturing testosterone-family hormones from the raw materials already circulating in the body.

If you or someone you love is managing advanced prostate cancer, or trying to understand why hormone therapy can eventually stop working, this is a genuinely new piece of the puzzle, not a reason to change anything about a current treatment plan.

Key takeaways:

• Researchers identified two new bacterial genes, desF and desG, that let specific gut and urinary bacteria convert steroid hormone precursors into testosterone-family hormones.
• In a 69-person patient cohort, men whose advanced prostate cancer was progressing on abiraterone/prednisone therapy had higher desF levels in their stool than men not yet on hormone therapy.
• Abiraterone blocks the body's own androgen-making enzyme but does not block the bacterial version, and prednisone (a steroid drug given alongside abiraterone) can itself be converted into androgens by these bacteria.
• The findings come from human samples and lab-grown cancer cells, not living patients or animals, so the study shows a plausible mechanism, not proof that these bacteria drive tumor growth in the body.

Two Bacterial Genes That Turn Steroid Precursors Into Testosterone

Researchers discovered two previously unknown bacterial genes, named desF and desG, that let certain bacteria manufacture hormones from the same family as testosterone. The gene desF sits in Clostridium scindens, a bacterium that lives in many human guts, and it encodes an enzyme called 17-alpha-hydroxysteroid dehydrogenase (a protein that rearranges a hormone precursor's chemical structure). That enzyme converts androstenedione (a hormone precursor the adrenal glands normally make) into epitestosterone, a hormone in the testosterone family.

The second gene, desG, was found in Propionimicrobium lymphophilum, a bacterium recovered from urine and prostate tissue. It encodes a related enzyme, 17-beta-hydroxysteroid dehydrogenase, that converts a similar precursor (11-beta-hydroxy-androstenedione) into 11-beta-hydroxytestosterone. To confirm this was not a fluke of one bacterial strain, the team sequenced 14 newly collected strains of C. scindens and compared them with 20 more pulled from public genome databases, finding the same genetic pathway repeatedly. Together, desF and desG show that bacteria living in and on the human body can run their own small hormone-producing pathways, independent of the glands the body normally relies on.

Why This Matters for Men on Abiraterone Therapy

This discovery matters most for men with advanced prostate cancer taking abiraterone plus prednisone (AA/P), a standard hormone-blocking combination, because the drug built to cut off the body's own testosterone supply does not touch the bacterial pathway the study describes. Abiraterone works by blocking a host enzyme called CYP17A1, which the body needs to manufacture androgens in the adrenal glands. The researchers found that abiraterone does not inhibit the bacterial version of that enzyme (called bacterial desmolase), meaning these bacteria could keep converting steroid precursors into androgens even while the drug is doing exactly what it was designed to do to the body's own hormone factories.

There is a further twist: prednisone, the steroid medication typically given alongside abiraterone to offset its side effects, can itself be converted into androgens by the same bacterial enzymes. In lab experiments using LNCaP and VCaP (two standard prostate cancer cell lines), the bacterially produced hormones drove significant cell growth, an effect that depended on the androgen receptor (the cell's docking site for testosterone-family hormones), since blocking that receptor shut the growth down. This gives researchers a specific, testable explanation for a problem oncologists already see clinically: prostate cancer that keeps growing on AA/P therapy even though the drug is suppressing the body's own hormone production, a resistance pattern reviewed in detail in the broader literature on gut microbiome contributions to prostate cancer.

Testing Stool, Urine, and Prostate Tissue From 69 Patients

The team built its case in layers, starting with pure bacterial cultures and ending with real patient samples. They first grew C. scindens and P. lymphophilum in the lab alongside steroid precursors to confirm the enzymes worked as predicted, then tested human material. The fecal cohort included 69 men total: 25 with hormone-sensitive prostate cancer who had not yet started hormone therapy, compared against 44 with advanced prostate cancer already on abiraterone/prednisone. Stool desF levels were measurably higher in the group whose cancer was progressing on AA/P therapy than in the untreated comparison group.

A separate urine analysis looked at men about to undergo a prostate biopsy: androgen-producing bacteria were recovered from 8 of 25 pre-biopsy samples (four of those men were later diagnosed with prostate cancer), compared with just 2 of 14 age-matched healthy controls. No animal models were used anywhere in the study. Everything traces back to bacterial cultures, human stool and urine samples, prostate tissue, and cancer cells grown in dishes, a design that is well suited to establishing a mechanism but not to proving what happens inside a living body over time. Reviews of abiraterone resistance mechanisms in general have long flagged that drug-resistant tumors can find alternative routes to androgen supply; this study adds a specific, previously unrecognized bacterial route to that list.

What This Means If You or a Family Member Is on Hormone Therapy

For men currently on abiraterone/prednisone, or anyone researching why prostate cancer therapy sometimes stops working, the honest answer right now is that this is new mechanistic evidence, not a new test or treatment. Nothing here suggests changing a probiotic, diet, or supplement routine, and nothing in the study identifies a specific bacterial strain that should be avoided or targeted at home. What it does offer is a concrete question worth raising with an oncologist if a case of AA/P-treated prostate cancer starts progressing despite the drug working as expected: whether gut or urinary bacteria are an active area of investigation for that specific patient's resistance pattern. The study itself does not provide a clinical test for this yet.

The Open Question: Correlation, Not Proof of Cause

The central limitation is one the researchers themselves flagged: elevated fecal desF in men progressing on AA/P therapy is an association, not evidence that the bacteria caused the progression. Patients with more of these bacteria and patients with worsening cancer were found together; the study does not show that removing or suppressing the bacteria would change the disease course. The cell-line experiments demonstrating that bacterially produced hormones can drive prostate cancer cell growth were done in dishes, not in the body, so whether bacterially made androgens actually reach and act on a tumor inside a living patient remains unproven. Sample sizes in the subgroups (44 patients, 8 positive urine samples) are also modest, which is normal for this stage of mechanistic research but means the specific numbers should be read as suggestive rather than definitive.

What Comes Next for Bacterial Androgen Research

The natural next steps for this line of research, based on the gap the study leaves open, are validating the fecal desF association in larger and more diverse patient groups, developing a reliable way to measure bacterial androgen-producing capacity in a clinical setting, and testing whether blocking the bacterial desmolase, desF, or desG enzymes changes treatment outcomes, a strategy other work on gut microbiome contributions to androgen production and treatment resistance has also flagged as a priority. No timeline for any of that has been established or reported.

Common Questions

Can gut bacteria actually cause prostate cancer? No. The study shows certain bacteria can manufacture testosterone-family hormones and that this is associated with treatment resistance, but it does not show the bacteria cause prostate cancer to develop in the first place.

Does this mean abiraterone doesn't work? No. Abiraterone still blocks the body's own hormone-producing enzyme as intended. The new finding is that a separate, bacterial version of a similar enzyme is unaffected by the drug, which may explain some but not all cases of treatment resistance.

Should someone on hormone therapy change their diet or take a probiotic because of this? No. The study does not test or support any dietary change, supplement, or probiotic as a way to affect this pathway, and doing so based on this research alone would be unproven and potentially unsafe without medical guidance.

What is epitestosterone, and why does it matter here? Epitestosterone is a hormone in the same family as testosterone that was previously assumed to be biologically weak. The study found it can drive prostate cancer cell growth about as effectively as testosterone itself, which was an unexpected result.

References

1. Taojun Wang, Saeed Ahmad, Raissa Santos de Lima Rosa, et al. (2025). The urinary pathobiont Actinobaculum massiliense generates androgens via the dirAB pathway. https://doi.org/10.64898/2025.12.18.695155
2. Taojun Wang, Saeed Ahmad, Angélica Cruz-Lebrón, et al. (2025). An expanded metabolic pathway for androgen production by commensal bacteria. Nature Microbiology. https://doi.org/10.1038/s41564-025-01979-9
3. Jing Huang, Xin-Hua Zhu, Lloyd C. Trotman, Che-Kai Tsao (2026). The Role of Gut Microbiome in Prostate Cancer: Current Evidence and Emerging Opportunities. Cancers. https://doi.org/10.3390/cancers18060998
4. Jan M. Moll, Jinpei Kumagai, Martin E. van Royen, et al. (2019). A bypass mechanism of abiraterone‐resistant prostate cancer: Accumulating CYP17A1 substrates activate androgen receptor signaling. The Prostate. https://doi.org/10.1002/pros.23799
5. Angelica Cruz Lebron, Pedro A Balbuena-Almodóvar, Luke Mummert, et al. (2025). SAT-312 Role of the gut microbiome in androgen production and prostate cancer treatment resistance. Journal of the Endocrine Society. https://doi.org/10.1210/jendso/bvaf149.2454