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An expanded metabolic pathway for androgen production by commensal bacteria
Taojun Wang1,2, Saeed Ahmad3,4, Angélica Cruz-Lebrón5
1Department of Animal Sciences, University of Illinois Urbana-Champaign, Urbana, IL, USA.
Nature Microbiology
|April 21, 2025
Summary
Gut and urinary bacteria produce androgens, influencing prostate cancer growth and abiraterone treatment response. Microbial genes like desF are key to this process.
Area of Science:
- Microbiology
- Endocrinology
- Cancer Biology
Background:
- Commensal bacteria influence host steroid hormones, including androgens.
- Microbial pathways for androgen production remain largely uncharacterized.
Purpose of the Study:
- Identify microbial genes involved in androgen synthesis.
- Investigate the role of microbial androgens in prostate cancer and drug metabolism.
Main Methods:
- Identified microbial gene desF in Clostridium scindens catalyzing androstenedione to epitestosterone conversion.
- Assessed epitestosterone's effect on prostate cancer cell proliferation in vitro.
- Analyzed stool desF levels in prostate cancer patients.
- Detected 17β-hydroxysteroid dehydrogenase activity (desG) in urinary bacteria.
- Investigated bacterial conversion of cortisol and prednisone to androgens.
Main Results:
- Epitestosterone promotes androgen receptor-dependent prostate cancer cell proliferation.
- Elevated stool desF levels correlate with non-response to abiraterone/prednisone therapy.
- Urinary bacteria produce androgens and promote prostate cancer cell growth via cortisol/prednisone metabolism.
- Bacterial desmolase (DesAB) is not inhibited by abiraterone, unlike host CYP17A1.
Conclusions:
- Microbial genes (desF, desG) contribute to androgen production in the gut and urinary tract.
- Bacterial androgenesis plays a role in prostate cancer progression and resistance to endocrine therapy.
- Targeting bacterial steroid metabolism may offer new therapeutic strategies for prostate cancer.
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