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.

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