This study provides a comprehensive analysis of *Anaerostipes hadrus* (A. hadrus), a dominant species in the human gut microbiota known for producing probiotic butyrate. However, recent studies suggest that A. hadrus may negatively impact host health by synthesizing fatty acids and metabolizing the anticancer drug 5-fluorouracil (5-FU). To better understand the complex role of A. hadrus, the authors integrated 527 high-quality public A. hadrus genomes and five distinct metagenomic cohorts. They identified 5-FU metabolism genes as ubiquitous in A. hadrus genomes, alongside butyrate-producing genes. Metagenomic analysis revealed that A. hadrus is widely distributed in healthy individuals, patients with inflammatory bowel disease (IBD), and colorectal cancer (CRC) patients, with higher abundance in healthy individuals. The study also confirmed that A. hadrus can convert 5-FU to α-fluoro-β-ureidopropionic acid (FUPA) through the preTA operon, encoding bacterial dihydropyrimidine dehydrogenase (EcDPD). In vitro assays validated the short-chain fatty acid production and 5-FU metabolism abilities of A. hadrus. The findings offer new insights into the evolutionary relationships, functional characteristics, prevalence, and potential applications of A. hadrus, highlighting its dual role in both beneficial and harmful effects on host health.This study provides a comprehensive analysis of *Anaerostipes hadrus* (A. hadrus), a dominant species in the human gut microbiota known for producing probiotic butyrate. However, recent studies suggest that A. hadrus may negatively impact host health by synthesizing fatty acids and metabolizing the anticancer drug 5-fluorouracil (5-FU). To better understand the complex role of A. hadrus, the authors integrated 527 high-quality public A. hadrus genomes and five distinct metagenomic cohorts. They identified 5-FU metabolism genes as ubiquitous in A. hadrus genomes, alongside butyrate-producing genes. Metagenomic analysis revealed that A. hadrus is widely distributed in healthy individuals, patients with inflammatory bowel disease (IBD), and colorectal cancer (CRC) patients, with higher abundance in healthy individuals. The study also confirmed that A. hadrus can convert 5-FU to α-fluoro-β-ureidopropionic acid (FUPA) through the preTA operon, encoding bacterial dihydropyrimidine dehydrogenase (EcDPD). In vitro assays validated the short-chain fatty acid production and 5-FU metabolism abilities of A. hadrus. The findings offer new insights into the evolutionary relationships, functional characteristics, prevalence, and potential applications of A. hadrus, highlighting its dual role in both beneficial and harmful effects on host health.