Even as medications work to suppress levels of male hormones, certain bacteria in the gut start their own hormone factory.

In some cancers, such as melanoma, the population of bacteria in the patient’s gut can predict how well that patient responds to immunotherapy. “In fact,” says microbiologist Karen Sfanos, Ph.D., a pioneer in studying the interplay between bacteria and cancer, “high-fiber diets as a means to promote ‘good gut bugs’ and even fecal transplants are being studied in clinical trials as means to improve therapeutic response.”

But this may not work the same in prostate cancer. A recent study led by Lauren Peiffer, D.V.M., Ph.D., in Sfanos’ laboratory, investigated this phenomenon as part of a clinical trial led by Oregon Health & Science University scientist Julie Graff, M.D. Participants in the study were patients with advanced prostate cancer who had taken enzalutamide and were beginning treatment with an immunotherapy drug called pembrolizumab. Peiffer analyzed bacteria in fecal samples collected before and during treatment.

“Surprisingly, the study found that many types of bacteria that may affect immunotherapy in other types of cancer were not linked to treatment response in prostate cancer,” says Sfanos. “However, we identified different types of bacteria,” including a species typically found in the mouth called Streptococcus salivarius, “that were more abundant in patients who had a response to therapy.” This study was recently published in the journal Neoplasia. -- https://pubmed.ncbi.nlm.nih.gov/35908379/

Gut bacteria and hormone production: Gut bugs may actively undercut treatment of advanced prostate cancer, and this is another major focus of Sfanos’ research. Even as androgen deprivation therapy (ADT) and androgen receptor (AR)-targeted treatment work to suppress levels of male hormones, certain bacteria in the gut start their own hormone factory! Gut bugs “can produce hormones that may interfere with hormonal therapy.” In 2018, (https://pubmed.ncbi.nlm.nih.gov/29988102/ ) Sfanos and colleagues reported that hormone-producing bacteria are more abundant in prostate cancer patients who are on ADT or AR-targeted therapy. A groundbreaking study by UK scientists recently confirmed these findings, and in mice with castration-resistant prostate cancer, they found a buildup of hormone-producing bacteria that make the disease worse.

The Sfanos lab has been collecting samples for use in microbiome studies since 2016. In one study, Sfanos, postdoctoral fellow Angélica Cruz-Lebrón, Ph.D., postbaccalaureate fellow Pedro Balbuena-Almodóvar, and collaborators are looking at clinical samples collected from prostate cancer patients undergoing treatment with abiraterone acetate (Zytiga). This project, funded by the Prostate Cancer Foundation and the Department of Defense Prostate Cancer Research Program, will measure hormone levels in fecal and serum samples as patients undergo treatment and will correlate these levels with treatment response. Ultimately, these studies aim to identify a microbial drug target that can make treatment for advanced prostate cancer more effective.