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 C. elegans 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 E. coli and the nematode C. elegans 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.

人体微生物组（human microbiome）可调控治疗药物的疗效，但细菌与药物的互作在寿命调控中的作用仍未得到充分阐明。本研究利用剪接衰老标志物（splicing aging marker）开展大规模药物筛选，鉴定出一种氟嘧啶类衍生物——氟尿苷（doxifluridine），该物质可延长秀丽隐杆线虫（C. elegans）的寿命与健康寿命，并延缓人类细胞衰老。值得注意的是，氟尿苷对寿命延长的调控效果依赖于细菌菌株。本研究结合大肠杆菌（E. coli）与秀丽隐杆线虫模型，采用四向筛选策略，阐明了氟尿苷、营养物质、微生物与宿主寿命之间的互作关系。研究证实，细菌的核糖核苷酸代谢可调控氟尿苷的转化过程，进而调节宿主寿命。此外，氟尿苷可改变细菌代谢产物，如亚油酸（linoleic acid）与胍丁胺（agmatine）的组成，这类代谢产物同样会对宿主寿命产生影响。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。