Danping Liu, Li-Sheng Xie, Shitao Lian, Kexin Li, Yun Yang, Wen-Zhao Wang, Songnian Hu, Shuang-Jiang Liu, Chang Liu, Zilong He
() is a dominant species in the human gut microbiota and considered a beneficial bacterium for producing probiotic butyrate. However, recent studies have suggested that may negatively affect the host through synthesizing fatty acid and metabolizing the anticancer drug 5-fluorouracil, indicating that the impact of is complex and unclear. Therefore, comprehensive genomic studies on need to be performed. We integrated 527 high-quality public genomes and five distinct metagenomic cohorts. We analyzed these data using the approaches of comparative genomics, metagenomics, and protein structure prediction. We also performed validations with culture-based assays. We constructed the first large-scale pan-genome of ( = 527) and identified 5-fluorouracil metabolism genes as ubiquitous in genomes as butyrate-producing genes. Metagenomic analysis revealed the wide and stable distribution of in healthy individuals, patients with inflammatory bowel disease, and patients with colorectal cancer, with healthy individuals carrying more . The predicted high-quality protein structure indicated that might metabolize 5-fluorouracil by producing bacterial dihydropyrimidine dehydrogenase (encoded by the operon). Through assays, we validated the short-chain fatty acid production and 5-fluorouracil metabolism abilities of . We observed for the first time that can convert 5-fluorouracil to ��-fluoro-��-ureidopropionic acid, which may result from the combined action of the operon and adjacent (encoding bacterial dihydropyrimidinase). Our results offer novel understandings of , exceptionally functional features, and potential applications.
IMPORTANCE: This work provides new insights into the evolutionary relationships, functional characteristics, prevalence, and potential applications of .
