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Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
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Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
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Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
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Journal Article
Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
2020
Overview
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.
Abiraterone acetate (AA) is indicated for the treatment of patients with metastatic castrate-resistant prostate cancer. Here, the authors show that, in prostate cancer patients, orally administered AA remodels the gut microbiome and promotes the enrichment of the commensal bacterium
Akkermansia muciniphila
at the expense of androgen-utilizing
Corynebacterium
species.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 45/77
/ 45/88
/ 49/22
/ 49/23
/ 49/40
/ 49/56
/ Abiraterone Acetate - metabolism
/ Abiraterone Acetate - pharmacology
/ Abiraterone Acetate - therapeutic use
/ Androgen Antagonists - pharmacology
/ Bacteria
/ Gastrointestinal Microbiome - drug effects
/ Humanities and Social Sciences
/ Humans
/ Male
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms, Castration-Resistant - drug therapy
/ RNA, Ribosomal, 16S - genetics
/ Science
/ Verrucomicrobia - drug effects
