Anaerostipes hadrus , a butyrate-producing bacterium capable of metabolizing 5-fluorouracil

作者：Danping Liu, Lisheng Xie, Shitao Lian, Kexin Li, Yun Yang, Wen-Zhao Wang, Songnian Hu, Shuang‐Jiang Liu, Chang Liu, Zilong He · 发表于：mSphere · 年份：2024 · DOI：10.1128/msphere.00816-23 · 被引用次数：58 · 研究领域：Gut microbiota and health、Pancreatic and Hepatic Oncology Research、Biochemical and Molecular Research

ABSTRACT Anaerostipes hadrus ( A. hadrus ) is a dominant species in the human gut microbiota and considered a beneficial bacterium for producing probiotic butyrate. However, recent studies have suggested that A. hadrus may negatively affect the host through synthesizing fatty acid and metabolizing the anticancer drug 5-fluorouracil, indicating that the impact of A. hadrus is complex and unclear. Therefore, comprehensive genomic studies on A. hadrus need to be performed. We integrated 527 high-quality public A. hadrus 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 in vitro assays. We constructed the first large-scale pan-genome of A. hadrus ( n = 527) and identified 5-fluorouracil metabolism genes as ubiquitous in A. hadrus genomes as butyrate-producing genes. Metagenomic analysis revealed the wide and stable distribution of A. hadrus in healthy individuals, patients with inflammatory bowel disease, and patients with colorectal cancer, with healthy individuals carrying more A. hadrus . The predicted high-quality protein structure indicated that A. hadrus might metabolize 5-fluorouracil by producing bacterial dihydropyrimidine dehydrogenase (encoded by the preTA operon). Through in vitro assays, we validated the short-chain fatty acid production and 5-fluorouracil metabolism abilities of A. hadrus . We observed for...