Abiraterone acetate (AA), an androgen biosynthesis inhibitor, shows efficacy against androgen-independent prostate cancer beyond its known mechanism. This study reveals that androgen deprivation therapy depletes androgen-utilizing *Corynebacterium* spp., while oral AA enriches the beneficial commensal *Akkermansia muciniphila*. Increased bacterial vitamin K2 biosynthesis, an inhibitor of androgen-dependent and -independent tumor growth, coincides with *A. muciniphila* enrichment. Host-free gut models confirm these findings, suggesting a direct microbe-drug interaction. AA is metabolized by bacteria, with breakdown products selectively impacting bacterial growth. *A. muciniphila* is identified as a key regulator of AA's effects on gut microbiota, potentially impacting treatment response. Targeted delivery of bacterial growth agents may be a promising avenue for future cancer therapies.
Publisher
Nature Communications
Published On
Sep 24, 2020
Authors
Brendan A. Daisley, Ryan M. Chanyi, Kamilah Abdur-Rashid, Kait F. Al, Shaeley Gibbons, John A. Chmiel, Hannah Wilcox, Gregor Reid, Amanda Anderson, Malcolm Dewar, Shiva M. Nair, Joseph Chin, Jeremy P. Burton
Tags
Abiraterone acetate
prostate cancer
gut microbiome
Akkermansia muciniphila
vitamin K2
microbe-drug interaction
bacterial growth agents
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