Caenorhabditis elegans strain:N2 Transcriptome or Gene expression
Increasing evidence implicates that human microbiome can modulate the efficacy of therapeutic drugs. However, the bacteria-drug interaction modulates longevity is not largely studied. Here, through large-scale drug screen using splicing aging marker, we identified that a fluoropyrimidine derivative doxifluridine extends lifespan and healthspan in C. elegans and ameliorate the human cellular senescence. Interestingly, the effect of doxifluridine on lifespan extension dependent on bacteria strains. Combining the bacteria E. coli and nematode C. elegans model, we used four-way screen strategy to understand the interaction between doxifluridine, nutrient, microbe and host longevity. We show that bacteria ribonucleotide metabolism can modulate doxifluridine conversion to regulates host lifespan. On the other side, doxifluridine affects metabolites in bacteria such as linoleic acid and agmatine, which regulates host lifespan. These findings provide the potential role of bacteria in regulating fluoropyrimidine effect on host longevity.