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How does advanced prostate cancer continue to grow, despite hormone therapy? A new study implicates bacteria in the gut that make testosterone, fueling the tumor. This groundbreaking insight may also offer a new approach to treatment.

While the vast majority of prostate cancer is treatable, in 2021, nearly 34,000 patients are estimated to die of the disease – most of an advanced form known as castration-resistant prostate cancer (CRPC). These tumors continue to grow and spread, even as their “fuel supply”—testosterone—is lowered by androgen deprivation therapy (ADT). To date, the reasons behind progression to CRPC are not completely known, but a closer look into our gut microbiota, or “bugs in the gut,” may provide some answers.

According to a recent PCF-funded study by Pernigoni and colleagues published in the prestigious journal Science, when you start on ADT, bacteria in your gut can start making testosterone. This can provide prostate cancer cells with an alternative “fuel supply,” resulting in a cancer that can continue to grow.

Normally, trillions of bacteria and other micro-organisms live on and in our bodies, largely benefiting us through functions such as helping to digest our food and regulate our immune system. But certain bacteria may have dangerous consequences for some patients with prostate cancer.

Through an elegant series of studies in mice and in patients with prostate cancer, the researchers demonstrated the complex relationships among gut bacteria, hormone levels, patient outcomes, and even antibiotic therapy. They found that patients with prostate cancer on ADT had higher amounts of certain types of bacteria (Akkermansia and Ruminococcus) that have the ability to make androgens. When these “bad” gut bacteria—the ones making testosterone—were transplanted from patients with CRPC into mice with hormone-sensitive prostate cancer, the researchers saw tumors grow and become resistant to treatment. On the other hand, some bacterial species appear to be beneficial. In patients, having more Prevotella bacteria in the gut was linked to improved survival.

The researchers also tested the effect of antibiotics in mouse models of prostate cancer. Treating these mice with antibiotics killed off gut bacteria…..and slowed tumor progression. Similarly, giving mice more Prevotella bacteria also slowed tumor growth.

Looking ahead, bacterial “fingerprints” may identify men with gut microbiota who may benefit from intervention. Although much more work needs to be done in humans to ensure efficacy and safety, this may eventually lead to use of fecal transplant of “good bacteria” or antibiotic therapy. Patients with prostate cancer may someday be able to take a sort of “yogurt drink” enriched with “good” bacteria to counter the production of androgens.

Other questions remain unanswered. For example: how do gut bacteria sense low testosterone, triggering them to synthesize the hormone? Uncovering the mysteries behind CRPC is critical to the fight against this disease. If these findings on androgen-producing gut bacteria bear out in the clinic, doctors and patients may have new—and perhaps unexpected—defenses.