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Record W3088710714 · doi:10.1038/s41467-020-18649-5

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

2020· article· en· W3088710714 on OpenAlexafffund
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 L. Chin, Jeremy P. Burton

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGut microbiota and health
Canadian institutionsSt Joseph's Health CareCanadian Science Centre for Human and Animal HealthLawson Health Research InstituteWestern University
FundersJanssen PharmaceuticalsNational Research Council CanadaW. Garfield Weston FoundationGovernment of CanadaCanadian Urological Oncology Group
KeywordsAkkermansia muciniphilaProstate cancerAndrogenCancer researchBiologyProstateAbiraterone acetateCancerInternal medicineMedicineEndocrinologyGut floraImmunologyAndrogen deprivation therapyHormone

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.029
GPT teacher head0.314
Teacher spread0.285 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations134
Published2020
Admission routes2
Has abstractyes

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