Evidence map›Paper›PMID 36138165›Full record

ArticleNature microbiology2022

Host and gut bacteria share metabolic pathways for anti-cancer drug metabolism.

Peter Spanogiannopoulos, Than S Kyaw, Ben G H Guthrie, Patrick H Bradley, Joyce V Lee, Jonathan Melamed, Ysabella Noelle Amora Malig, Kathy N Lam, Daryll Gempis, Moriah Sandy and 8 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature microbiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed
8.0field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

77 citing papers in PubMed, 102 citations in OpenAlex.

  1. Trial
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  7. Microbiome-guided cancer immunotherapy: immune mechanisms, resistance pathways, and translational opportunities for precision oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  8. Review
  9. Review
  10. Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026
    Review
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. Review
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17 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors at 2 institutions in 1 country.

Peter Spanogiannopoulos *Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Than S Kyaw *Department of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7933-8615
Ben G H GuthrieDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9694-7263
Patrick H BradleyGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9231-8344
Joyce V LeeDepartment of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.
Jonathan MelamedClinical Toxicology and Environmental Biomonitoring Laboratory, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-5981-7766
Ysabella Noelle Amora MaligClinical Toxicology and Environmental Biomonitoring Laboratory, University of California San Francisco, San Francisco, CA, USA.
Kathy N LamDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Daryll GempisDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA.
Moriah SandyDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Wesley KidderDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Erin L Van BlariganUCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Chloe E AtreyaDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Alan VenookDepartment of Medicine, University of California San Francisco, San Francisco, CA, USA.
Roy R GeronaClinical Toxicology and Environmental Biomonitoring Laboratory, University of California San Francisco, San Francisco, CA, USA.
Andrei GogaDepartment of Cell and Tissue Biology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9127-0986
Katherine S PollardGladstone Institutes, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9870-6196
Peter J TurnbaughDepartment of Microbiology and Immunology, University of California San Francisco, San Francisco, CA, USA. Peter.Turnbaugh@ucsf.edu.ORCID http://orcid.org/0000-0002-0888-2875
University of California, San Francisco · USGladstone Institutes · US

Funding

Molecular and Cellular Mechanisms in CancerT32CA108462 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2004 to 2024
$10.4M
Predicting and preventing drug metabolism by the human gut microbiomeR01HL122593 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Peter James Turnbaugh · 2016 to 2026
$5.7M
Uncovering Mechanisms of Regulation and Dependency on Fatty Acid Oxidation in MYC-Driven TumorsR01CA223817 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GOGA, ANDREI · 2018 to 2022
$1.8M
(PQ10) Harnessing the human gut microbiome to predict chemotherapy outcomesR21CA227232 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI ATREYA, CHLOE E., TURNBAUGH, PETER JAMES · 2018 to 2019
$378k
Impact of the microbiome on chemotherapeutic outcomesF30CA257378 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KYAW, THAN SOE · 2021 to 2024
$190k
Elucidating metabolic functions of PIM Kinase in breast cancer growth and metastasisF32CA243548 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI LEE, JOYCE VIVIAN · 2019 to 2022
$187k
NCI NIH HHS F30 CA257378NCI NIH HHS F32 CA243548NCI NIH HHS R01 CA223817NCI NIH HHS R21 CA227232NCI NIH HHS T32 CA108462NHLBI NIH HHS R01 HL122593
6 · The paper itself

Abstract

Pharmaceuticals have extensive reciprocal interactions with the microbiome, but whether bacterial drug sensitivity and metabolism is driven by pathways conserved in host cells remains unclear. Here we show that anti-cancer fluoropyrimidine drugs inhibit the growth of gut bacterial strains from 6 phyla. In both Escherichia coli and mammalian cells, fluoropyrimidines disrupt pyrimidine metabolism. Proteobacteria and Firmicutes metabolized 5-fluorouracil to its inactive metabolite dihydrofluorouracil, mimicking the major host mechanism for drug clearance. The preTA operon was necessary and sufficient for 5-fluorouracil inactivation by E. coli, exhibited high catalytic efficiency for the reductive reaction, decreased the bioavailability and efficacy of oral fluoropyrimidine treatment in mice and was prevalent in the gut microbiomes of colorectal cancer patients. The conservation of both the targets and enzymes for metabolism of therapeutics across domains highlights the need to distinguish the relative contributions of human and microbial cells to drug efficacy and side-effect profiles.

Indexed as

Antineoplastic AgentsEscherichia coliAnimalsBacteriaFluorouracilHumansMammalsMetabolic Networks and PathwaysMiceAntineoplastic AgentsFluorouracil

Identifiers

PMID36138165
PMCPMC9530025
OpenAlexW4296690274

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.