Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients
Abstract 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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2020-09-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-020-18649-5 |
| _version_ | 1797836441884033024 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Brendan A. Daisley |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-09T15:08:59Z |
| format | Article |
| id | doaj.art-d057b42a310240ed8e3bbeaf06f35107 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-04-09T15:08:59Z |
| publishDate | 2020-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-d057b42a310240ed8e3bbeaf06f351072023-04-30T11:19:51ZengNature PortfolioNature Communications2041-17232020-09-0111111110.1038/s41467-020-18649-5Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patientsBrendan A. Daisley0Ryan M. Chanyi1Kamilah Abdur-Rashid2Kait F. Al3Shaeley Gibbons4John A. Chmiel5Hannah Wilcox6Gregor Reid7Amanda Anderson8Malcolm Dewar9Shiva M. Nair10Joseph Chin11Jeremy P. Burton12Department of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Microbiology and Immunology, The University of Western OntarioDepartment of Surgery, Division of Urology, Schulich School of MedicineDepartment of Surgery, Division of Urology, Schulich School of MedicineDepartment of Surgery, Division of Urology, Schulich School of MedicineDepartment of Surgery, Division of Urology, Schulich School of MedicineDepartment of Microbiology and Immunology, The University of Western OntarioAbstract 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.https://doi.org/10.1038/s41467-020-18649-5 |
| spellingShingle | 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 Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients Nature Communications |
| title | Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients |
| title_full | Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients |
| title_fullStr | Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients |
| title_full_unstemmed | Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients |
| title_short | Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients |
| title_sort | abiraterone acetate preferentially enriches for the gut commensal akkermansia muciniphila in castrate resistant prostate cancer patients |
| url | https://doi.org/10.1038/s41467-020-18649-5 |
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