Scientists Discover Bacteria That Can Make Testosterone Near the Prostate, With Potential Implications for Cancer

A newly discovered bacterial pathway turns a common steroid precursor into testosterone.

by · ZME Science
Illustration made with the help of AI. Credit: ZME Science.

The prostate relies on testosterone to regulate normal growth, development and function. But in some situations, this natural relationship can grow to become totally dysfunctional. For instance, many prostate cancer cells use testosterone as a growth signal. The hormone binds to androgen receptors in the cells and switches on genes that help the tumor survive and multiply, which is why advanced cancers are often treated by lowering androgen levels or blocking that receptor.

Testosterone is normally made mostly by the testes, with smaller amounts of androgen precursors coming from the adrenal glands and being converted into active hormones by the body’s own enzymes. Now, a new study suggests there may be another, previously overlooked route. Bacteria living in the urinary tract can also perform some of that chemistry and produce testosterone.

In their new Nature Communications study, researchers report that Actinobaculum massiliense can take DHEA, a relatively weak steroid precursor made by the body, and convert it into testosterone. The team also identified two bacterial genes behind the process and used molecular simulations to explain how their enzymes work.

That’s not to say this bacterium causes prostate cancer, or even that it makes meaningful amounts of testosterone inside a person. But it reveals a previously unknown source of androgen production in the urinary tract, close to the prostate and potentially relevant to a disease driven by those hormones.

“We are not saying that these bacteria cause cancer,” said Rafael Bernardi, an Auburn University physicist and study co-author. “What we now know is that they possess the molecular machinery to produce testosterone. Because prostate cancer is so closely connected to androgen signaling, that is something worth understanding.”

A microbial testosterone factory

For much of the 20th century, doctors treated healthy urine as essentially sterile, assuming bacteria appeared there mainly during infections. More sensitive culture techniques and DNA sequencing turned the assumption on its head, revealing that the bladder and urinary tract harbor their own low-abundance microbial communities. We now know this bacterial community as the “urobiome,” and researchers are only now beginning to understand what those microbes actually do.

A 2018 study published in the Journal of Urology found diverse bacterial populations in men undergoing prostate biopsy, although it found no simple community-wide signature separating cancer from benign cases. A larger 2022 European Urology Oncology study later linked certain anaerobic bacteria in urine and prostate samples with higher-risk disease, while stressing that it had not established a functional connection to cancer.

The new work tries to supply some of that missing function.

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Diagram showing DHEA hormone pathway, testosterone synthesis, and bacterial culture of Actinobacteria massiliense. Credit: Nature Communications, 2026.

Researchers collected urine from 27 men before prostate biopsy and cultured bacteria from the samples. Nine carried bacteria with steroid-processing activity. And seven of those nine men were later diagnosed with prostate cancer. Three A. massiliense strains came from three men who received cancer diagnoses. Those numbers are intriguing, but the experiment was small and was not designed to determine whether the bacterium raises cancer risk.

The researchers then fed one strain DHEA. Over 72 hours, DHEA levels fell while testosterone rose to about 17 micromoles per liter. The bacterium could reach testosterone through either of two intermediate steroids, androstenedione or androstenediol.

Genome sequencing later pointed to two genes, which the team named dirA and dirB.

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Why prostate cancer researchers care

DirA appears to give the bacterium most of the chemical flexibility needed to turn DHEA into testosterone. The enzyme’s unusually open binding pocket lets the steroid rotate so that different parts of the molecule can be modified in sequence. That means a single bacterial enzyme can carry out several steps that, in humans, are normally split among different enzymes. DirB is much more limited because its narrow pocket often holds the steroid in the wrong position for those reactions.

This explains how A. massiliense can complete the pathway from DHEA to testosterone at all. The DirA gene is not merely another steroid-binding protein, but the key multipurpose enzyme that allows the bacterium to perform several hormone-conversion steps with the same molecular machinery.

“At this scale, chemistry depends on choreography,” Bernardi said. “The steroid has to be in the right place, facing the right way, at the right moment. One enzyme gives it room to do that. The other does not.”

The new study complements a 2025 Nature Microbiology study from some of the same researchers, which showed that other commensal bacteria could convert cortisol or prednisone into androgens and that bacterial steroid metabolism could stimulate prostate cancer cells in laboratory experiments. That line of research attracts attention because, as the National Cancer Institute explains, suppressing androgen production or blocking androgen receptors remains central to treating many prostate cancers.

Still, the leap from a flask to a tumor is enormous. Scientists do not yet know whether A. massiliense activates this pathway inside the urinary tract itself, how much testosterone it could make there, whether the hormone could reach prostate tissue or whether it would alter treatment response.

“The next step is to move from molecular capability to physiological relevance,” Bernardi said. “We now understand how the bacterial enzymes can perform the chemistry. The larger question is whether that chemistry has a meaningful effect in the complex environment of the human body.”