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Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion.

Publication ,  Journal Article
Ke, W; Saba, JA; Yao, C-H; Hilzendeger, MA; Drangowska-Way, A; Joshi, C; Mony, VK; Benjamin, SB; Zhang, S; Locasale, J; Patti, GJ; Lewis, N ...
Published in: Nat Commun
May 22, 2020

The gut microbiota metabolizes drugs and alters their efficacy and toxicity. Diet alters drugs, the metabolism of the microbiota, and the host. However, whether diet-triggered metabolic changes in the microbiota can alter drug responses in the host has been largely unexplored. Here we show that dietary thymidine and serine enhance 5-fluoro 2'deoxyuridine (FUdR) toxicity in C. elegans through different microbial mechanisms. Thymidine promotes microbial conversion of the prodrug FUdR into toxic 5-fluorouridine-5'-monophosphate (FUMP), leading to enhanced host death associated with mitochondrial RNA and DNA depletion, and lethal activation of autophagy. By contrast, serine does not alter FUdR metabolism. Instead, serine alters E. coli's 1C-metabolism, reduces the provision of nucleotides to the host, and exacerbates DNA toxicity and host death without mitochondrial RNA or DNA depletion; moreover, autophagy promotes survival in this condition. This work implies that diet-microbe interactions can alter the host response to drugs without altering the drug or the host.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 22, 2020

Volume

11

Issue

1

Start / End Page

2587

Location

England

Related Subject Headings

  • Uracil Nucleotides
  • Thymidine
  • Serine
  • Gastrointestinal Microbiome
  • Food-Drug Interactions
  • Folic Acid
  • Floxuridine
  • Escherichia coli
  • Dietary Supplements
  • Caenorhabditis elegans
 

Citation

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Ke, W., Saba, J. A., Yao, C.-H., Hilzendeger, M. A., Drangowska-Way, A., Joshi, C., … O’Rourke, E. J. (2020). Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun, 11(1), 2587. https://doi.org/10.1038/s41467-020-16220-w
Ke, Wenfan, James A. Saba, Cong-Hui Yao, Michael A. Hilzendeger, Anna Drangowska-Way, Chintan Joshi, Vinod K. Mony, et al. “Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion.Nat Commun 11, no. 1 (May 22, 2020): 2587. https://doi.org/10.1038/s41467-020-16220-w.
Ke W, Saba JA, Yao C-H, Hilzendeger MA, Drangowska-Way A, Joshi C, et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun. 2020 May 22;11(1):2587.
Ke, Wenfan, et al. “Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion.Nat Commun, vol. 11, no. 1, May 2020, p. 2587. Pubmed, doi:10.1038/s41467-020-16220-w.
Ke W, Saba JA, Yao C-H, Hilzendeger MA, Drangowska-Way A, Joshi C, Mony VK, Benjamin SB, Zhang S, Locasale J, Patti GJ, Lewis N, O’Rourke EJ. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nat Commun. 2020 May 22;11(1):2587.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

May 22, 2020

Volume

11

Issue

1

Start / End Page

2587

Location

England

Related Subject Headings

  • Uracil Nucleotides
  • Thymidine
  • Serine
  • Gastrointestinal Microbiome
  • Food-Drug Interactions
  • Folic Acid
  • Floxuridine
  • Escherichia coli
  • Dietary Supplements
  • Caenorhabditis elegans