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

Author

Listed:
  • Brendan A. Daisley

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Ryan M. Chanyi

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Kamilah Abdur-Rashid

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Kait F. Al

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Shaeley Gibbons

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • John A. Chmiel

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Hannah Wilcox

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Gregor Reid

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London)

  • Amanda Anderson

    (Schulich School of Medicine)

  • Malcolm Dewar

    (Schulich School of Medicine)

  • Shiva M. Nair

    (Schulich School of Medicine)

  • Joseph Chin

    (Schulich School of Medicine)

  • Jeremy P. Burton

    (The University of Western Ontario
    Canadian Centre for Human Microbiome and Probiotics Research
    St. Joseph’s Health Care London
    Schulich School of Medicine)

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.

Suggested Citation

  • 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, 2020. "Abiraterone acetate preferentially enriches for the gut commensal Akkermansia muciniphila in castrate-resistant prostate cancer patients," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-18649-5
    DOI: 10.1038/s41467-020-18649-5
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    Cited by:

    1. Koji Hosomi & Mayu Saito & Jonguk Park & Haruka Murakami & Naoko Shibata & Masahiro Ando & Takahiro Nagatake & Kana Konishi & Harumi Ohno & Kumpei Tanisawa & Attayeb Mohsen & Yi-An Chen & Hitoshi Kawa, 2022. "Oral administration of Blautia wexlerae ameliorates obesity and type 2 diabetes via metabolic remodeling of the gut microbiota," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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