Carl R. Woese Institute for Genomic Biology

A study led by Jason Ridlon (MME) has revealed that bacteria in the urinary tract can turn corticosteroids into androgens—hormones that help prostate cancer grow. The research is published in Nature Microbiology.

Ridlon, Associate Professor of Animal Sciences, led the microbiological research and hypothesis development while Joseph Irudayaraj (CGD/EIRH), Professor of Bioengineering, developed the microbial bead technology used in the experiments.

Ridlon began this work in 2015, hypothesizing that gut and urinary tract bacteria contribute to hormone-driven cancer. “When we obtained our first isolate that generated androgens, we thought, ‘Eureka!’ The hypothesis has some plausibility,” he said. The bacteria converted drugs such as prednisone used in androgen-deprivation therapy into androgens, stimulating cancer cell growth.

Initial seed funding from the Cancer Center at Illinois was later boosted by grants from the National Cancer Institute, Prostate Cancer Foundation, and the Department of Defense. The team also collaborated with Karen Sfanos at Johns Hopkins University, a pioneer in studying the link between the microbiome and prostate cancer.

Challenges included growing diverse bacteria and securing early funding. “We were very fortunate that the Cancer Center at Illinois saw promise in our proposal,” Ridlon said.

The team identified two bacterial genes, desF and desG, that make hormone-like compounds. One big surprise was that a hormone called epitestosterone, thought to block cancer, actually caused prostate cancer cells to grow even more.

They also studied Propionimicrobium lymphophilum, linked to prostate cancer, which may contribute by producing androgens.

“Bacteria in our bodies are an overlooked part of our hormone system,” said Ridlon. His Sterolbiome Lab focuses on how microbes affect steroid hormones. This could lead to new treatments, such as drugs that block harmful bacterial hormones.

Irudayaraj said, “When we developed the microbial bead technology, we did not realize the broad impact of its applications. Saeed Ahmad, a bioengineering doctoral student in our team, however, was instrumental in extending the methods to encapsulate anaerobic bacteria in the beads–this formed the basis for all co-culture studies to assess the role of these class of microbes on prostate cancer proliferation.”

Irujayaraj also noted that the team’s work on prostate cancer can be extended to other hormonal cancers, such as breast cancer.

“It’s nice to know that our work is recognized by highly regarded experts in this field! This also highlights the importance of collaboration across disciplines,” Ridlon said about the publication.

Ridlon shared that the team is now focused on mapping additional bacterial pathways that metabolize steroids. “We’re in the process of describing these new pathways. More will follow when these are published!”

“We have shown that these beads can withstand pH variations in the gastro-intestinal tract. Our next steps are to make several cocktails of these steroid modulating microbes for experiments in animal models, taking it a step closer to translation,” added Irudayaraj.