Christian Jobin, Ph.D., the Gatorade Trust Professor of Medicine in the division of gastroenterology, hepatology & nutrition in the University of Florida College of Medicine, and Raad Gharaibeh, Ph.D., a research assistant professor in the division, have received a two-year $364,143 R21 grant from the National Cancer Institute to study the role of the gut microbiome in prostate cancer.
The study builds on their recent collaboration with the laboratory of Andrea Alimonti, M.D., head of molecular oncology at the Institute of Oncology Research in Switzerland, about the role of microbiota in castration-resistant prostate cancer. This type of prostate cancer continues to grow despite therapy to decrease levels of sex steroids, known as androgen deprivation therapy.
The UF team collaborated with Alimonti’s group on a recent study published in Science showing that androgen deprivation therapy in both mice and humans promoted the expansion of the gut bacteria Ruminococcus sp. and Bacteroides acidifaciens.
“Importantly, the Alimonti group showed that a pure culture of R. gnavus– and B. acidifaciens-type strains were capable of converting testosterone precursors into active testosterone, increasing its levels in patients and mice with castration-resistant prostate cancer and preventing complete suppression of testosterone during androgen deprivation therapy,” said Gharaibeh, who is a member of the Cancer Center’s Cancer Therapeutics & Host Response research program, co-led by Jobin. “The current study aims to computationally identify the androgen-related bacterial enzymes in the gut microbiome of patients with castration-resistant prostate cancer. It further aims to isolate bacterial species harboring those enzymes and functionally test their impact on androgen metabolism.”
The group hypothesizes that the gut microbiome of patients with prostate cancer, specifically castration-resistant prostate cancer, will harbor genes that play an important role in androgen biotransformation and biosynthesis. The team will perform the study by using computational approaches, a high-throughput bacterial culture system and isolation combined with MALDI-TOF mass spectrometry, and a mini-array bioreactor continuous flow culture system.
“We hope the knowledge we gain from this study will provide a rationale to develop therapeutic strategies aimed at eliminating bacterial species contributing to androgen production or preventing their androgen-related enzymatic activities,” Jobin said.
The UF team will collaborate on the project with Alimonti and Nicolo Pernigoni from the Institute of Oncology Research, who will provide stool of patients with castration-resident and castration-sensitive prostate cancer and quantify androgen levels from the mini-bioreactor studies.