Host-Microbe Co-metabolism Dictates Cancer Drug Efficacy in C. elegans.

ABSTRACT: Fluoropyrimidines are the first-line treatment for colorectal cancer, but their efficacy is highly variable between patients. We queried whether gut microbes, a known source of inter-individual variability, impacted drug efficacy. Combining two tractable genetic models, the bacterium E. coli and the nematode C. elegans, we performed three-way high-throughput screens that unraveled the complexity underlying host-microbe-drug interactions. We report that microbes can bolster or suppress the effects of fluoropyrimidines through metabolic drug interconversion involving bacterial vitamin B₆, B₉, and ribonucleotide metabolism. Also, disturbances in bacterial deoxynucleotide pools amplify 5-FU-induced autophagy and cell death in host cells, an effect regulated by the nucleos

SUBMITTER: Scott TA 

PROVIDER: S-EPMC5406385 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature