Biology subjects

Mbuvi, P.

Publications and source records attributed to Mbuvi, P..

3 recordsLinked to original sources

bioRxiv2026

The Urinary Tract Commensal Peptoniphilus spp. Encodes a Novel 17β-Hydroxysteroid Dehydrogenase

Microbial steroid metabolism represents an underappreciated extension of the vertebrate endocrine system, with growing evidence that host-associated microbes contribute to the diversity and bioavailability of sex steroids within human tissues. Emerging studies have linked microbial androgen metabolism to urinary microbiome composition and to resistance to androgen deprivation therapy (ADT) in prostate cancer. While microbial pathways capable of converting steroid precursors such as cortisol to androgens, via the steroid-17,20-desmolase pathway, such as DesG-mediated interconversion of androstenedione to testosterone have been reported, the diversity of enzymes mediating downstream androgen interconversion remains incompletely defined. Here, we investigate the androgen-forming capabilities of anaerobic bacteria from the male genitourinary microbiome, focusing on NADPH-dependent 17{beta}-hydroxysteroid dehydrogenases (17{beta}-HSDHs) that catalyze interconversion of androstenedione and testosterone. We isolated androgen-forming bacterial strains from human male urine and identified a previously uncharacterized 17{beta}-HSDH encoded by Peptoniphilus obesi, demonstrated that this enzyme catalyzes the NADPH-dependent reduction of androstenedione to testosterone and the reverse oxidation reaction. Sequence similarity searches further identified a homologous 17{beta}-HSDH in Anaerococcus, which was synthesized and functionally validated, revealing conserved activity despite low sequence identity to the previously characterized urinary tract enzyme DesG. The enzymes were found to have broad substrate specificity for C19 and C18 17keto- and 17{beta}-hydroxysteroids. Together, these findings expand the known diversity of microbial 17{beta}-HSDHs and identify previously unrecognized androgen-forming activities within the genitourinary microbiome. ImportanceMicrobial steroid-transforming pathways may provide a mechanism by which commensal anaerobes contribute to androgen availability in the genitourinary tract. By identifying novel 17{beta}-hydroxysteroid dehydrogenases from Peptoniphilus and Anaerococcus, genera repeatedly associated with prostate cancer, this study provides mechanistic insight into how microbial steroid metabolism may influence hormone-driven disease.

microbiology↗

bioRxiv2025

The urinary pathobiont Actinobaculum massiliense generates androgens via the dirAB pathway

While overlooked during the Human Microbiome Project, characterizing the urinary microbiota in health and disease is a new frontier in microbiome science. Recent studies have associated differential abundance of bacterial taxa including Propionimicrobium lymphophilum and Actinobaculum/Actinotignum spp. with prostate cancer. In this study, we collected urine from subjects prior to prostate biopsy and applied a novel Human Sterolbiome Discovery High-throughput (HSDH) assay to identify culturable urinary bacteria with the ability to generate androgens. Application of the HSDH assay to urine samples led to the isolation of eight P. lymphophilum strains positive for cortisol side-chain cleavage (steroid-17,20-desmolase), 17{beta}-HSDH activity, or both. In addition, we isolated three strains of Actinobaculum massiliense that encode DHEA isomerase reductase (dir) genes. The dirA gene encodes a novel 3{beta}/17{beta}-hydroxysteroid dehydrogenase/{Delta}4,5-isomerase and the dirB gene encodes a novel 17{beta}-hydroxysteroid dehydrogenase isoform. Structural prediction and molecular dynamics reveal probable catalytic mechanisms based on the shared catalytic triad but distinct binding pocket geometries of the DirA and DirB that describe their respective reactions. Phylogenetic analysis of DirA and DirB revealed homologs in urinary tract commensals as well as bacteria associated with steroid degradation found in aquatic and terrestrial environments. Taken together, the development of the HSDH assay and the identification of the dir pathway genes is a significant advance in microbial endocrinology, laying the methodological foundation and providing the molecular basis for understanding the role of urinary tract bacteria in host endocrine physiology.

microbiology↗

bioRxiv2024

An expanded metabolic pathway for androgen production by host-associated bacteria

A growing body of literature implicates host-associated microbiota in the modulation of circulating androgen levels in the host, which could have far-reaching implications for androgen-mediated diseases. However, the microbial genetic pathways involved in androgen production remain unknown. Here, we report the first host-associated microbial gene (desF) encoding an enzyme that catalyzes conversion of androstenedione to epitestosterone (epiT) in the gut bacterium, Clostridium scindens. Despite current dogma that epiT is a nuclear androgen-receptor (AR) antagonist, we demonstrate that epiT is a potent androgen, as assessed by its ability to promote prostate cancer cell growth and expression of prostate specific antigen (PSA). We then quantified the desF gene in fecal samples collected from individuals with advanced prostate cancer (rising blood PSA) undergoing androgen deprivation therapy combined with abiraterone acetate and prednisone (AA/P). Strikingly, fecal desF levels were elevated in a subset of individuals progressing on AA/P versus samples taken during AA/P response (stable). Importantly, we observed that AA does not inhibit the bacterial desmolase enzyme that is analogous to the human drug target of AA. We then determined that bacterial isolates from urine or prostatectomy tissue are capable of androgen production. From these isolates we detected 17{beta}-hydroxysteroid dehydrogenase (17{beta}-HSDH) activity, which has not been previously reported in urinary tract bacteria, and discovered the desG gene in urinary isolates encoding 17{beta}-HSDH that catalyzed conversion of androstenedione to testosterone. Applying advanced artificial intelligence and molecular dynamics, we predict the structures and ligand binding to DesF and DesG. Using a novel bioengineered microencapsulation technique, we demonstrate that urinary androgen-producing bacterial strains can also promote prostate cancer cell growth through steroid metabolism. Taken together, our results are a significant advance for steroid microbiology in humans and suggest that these microbial biotransformations should be further studied in the context of androgen-mediated physiological processes and diseases.

microbiology↗