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Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion.
Ke, Wenfan; Saba, James A; Yao, Cong-Hui; Hilzendeger, Michael A; Drangowska-Way, Anna; Joshi, Chintan; Mony, Vinod K; Benjamin, Shawna B; Zhang, Sisi; Locasale, Jason; Patti, Gary J; Lewis, Nathan; O'Rourke, Eyleen J.
Afiliación
  • Ke W; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Saba JA; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Yao CH; Department of Chemistry, Washington University, St. Louis, MO, USA.
  • Hilzendeger MA; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Drangowska-Way A; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Joshi C; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
  • Mony VK; Department of Bioengineering, University of California, San Diego, La Jolla, CA, USA.
  • Benjamin SB; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Zhang S; Department of Biology, College of Arts and Sciences, University of Virginia, Charlottesville, VA, USA.
  • Locasale J; Department of Chemistry, Washington University, St. Louis, MO, USA.
  • Patti GJ; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA.
  • Lewis N; Department of Chemistry, Washington University, St. Louis, MO, USA.
  • O'Rourke EJ; Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. n4lewis@ucsd.edu.
Nat Commun ; 11(1): 2587, 2020 05 22.
Article en En | MEDLINE | ID: mdl-32444616
ABSTRACT
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.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Serina / Caenorhabditis elegans / Floxuridina / Interacciones Alimento-Droga / Microbioma Gastrointestinal Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Serina / Caenorhabditis elegans / Floxuridina / Interacciones Alimento-Droga / Microbioma Gastrointestinal Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2020 Tipo del documento: Article