Bacterial Route to Testosterone Production in Urobiome

Scientists have identified that Actinobaculum massiliense, a bacterium found in the human urinary tract, can convert the steroid precursor DHEA into testosterone under laboratory conditions. Published in Nature Communications in 2026, the study combined high-throughput screening, genomic sequencing, and atomic-level molecular simulations to understand this microbial pathway. The researchers discovered two genes responsible for this capability, named dirA and dirB for DHEA isomerase reductase. Through computational biophysics led by Auburn University, the team revealed that DirA features a broad, open pocket allowing versatile steroid transformations, whereas DirB possesses a narrow tunnel that restricts chemical reactions. While the finding does not prove that bacterial testosterone reaches prostate tumors or causes cancer, it introduces a novel microbial route for androgen production. This discovery raises important questions about whether urobiome metabolism shapes the chemical environment near the prostate and influences urinary steroid diagnostics. Researchers plan to move from molecular capability to physiological relevance by investigating how common the dirAB pathway is in human urinary microbiome datasets and determining its potential impact on prostate health and disease treatment responses.