E. coli metabolism raw data for research.

The human microbiome can modulate the efficacy of therapeutic drugs, but the role of bacteria-drug interactions in longevity is poorly understood. Here, we performed a large-scale drug screen using a splicing aging marker and identified a fluoropyrimidine derivative, doxifluridine, that extends lifespan and healthspan in <i>C. elegans</i> and attenuates human cellular senescence. Interestingly, the effect of doxifluridine on lifespan extension was dependent on bacterial strains. Using a four-way screen strategy that combined the bacteria <i>E. coli</i> and the nematode <i>C. elegans</i> model, we elucidated the interaction between doxifluridine, nutrient, microbe, and host longevity. We demonstrated that bacterial ribonucleotide metabolism modulated doxifluridine conversion and regulated host lifespan. Moreover, doxifluridine altered bacterial metabolites, such as linoleic acid and agmatine, which also affected host lifespan. These findings reveal the potential role of bacteria in mediating the anti-aging effect of fluoropyrimidine drugs.

人类微生物组可调节治疗药物的疗效，但细菌-药物互作在长寿调控中的作用仍知之甚少。本研究以可变剪接衰老标志物为筛选指标开展大规模药物筛选，鉴定出一种氟嘧啶类衍生物——去氧氟尿苷（doxifluridine），其可延长秀丽隐杆线虫（C. elegans）的寿命与健康寿命，并抑制人类细胞衰老。有趣的是，去氧氟尿苷对寿命延长的调控作用依赖于细菌菌株。本研究采用结合大肠杆菌（E. coli）与秀丽隐杆线虫模型的四向筛选策略，阐明了去氧氟尿苷、营养物质、微生物与宿主长寿之间的互作关系。研究证实，细菌的核糖核苷酸代谢可调控去氧氟尿苷的转化，进而调节宿主寿命。此外，去氧氟尿苷可改变细菌代谢产物（如亚油酸与胍丁胺），而这些代谢产物同样会影响宿主寿命。本研究结果揭示了细菌在介导氟嘧啶类药物抗衰老效应中的潜在作用。