Abiraterone acetate preferentially enriches for the gut commensal *Akkermansia muciniphila* in castrate-resistant prostate cancer patients

Abiraterone acetate (AA) is an inhibitor of androgen biosynthesis, though this cannot fully explain its efficacy against androgen-independent prostate cancer. Here, we demonstrate that androgen deprivation therapy depletes androgen-utilizing Corynebacterium spp. in prostate cancer patients and that oral AA further enriches for the health-associated commensal, Akkermansia muciniphila. Functional inferencing elucidates a coinciding increase in bacterial biosynthesis of vitamin K2 (an inhibitor of androgen dependent and independent tumor growth). These results are highly reproducible in a host-free gut model, excluding the possibility of immune involvement. Further investigation reveals that AA is metabolized by bacteria in vitro and that breakdown components selectively impact growth. We conclude that A. muciniphila is a key regulator of AA-mediated restructuring of microbial communities, and that this species may affect treatment response in castrate-resistant cohorts. Ongoing initiatives aimed at modulating the colonic microbiota of cancer patients may consider targeted delivery of poorly absorbed selective bacterial growth agents.

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