This study investigates the role of *Faecalibacterium prausnitzii* in coronary artery disease (CAD) and its potential as an antiatherosclerotic microbe. Through metagenomic sequencing and untargeted metabolomics, the researchers identified *F. prausnitzii* as a significant biomarker associated with CAD incidence across various patient groups. In vitro and in vivo experiments further revealed that *F. prausnitzii* mitigates inflammation and exhibits antiatherosclerotic effects in ApoE−/− mice by reducing intestinal LPS synthesis and strengthening mechanical and mucosal barriers. These findings suggest that *F. prausnitzii* may serve as a promising therapeutic target for preventing CAD by inhibiting atherosclerosis.This study investigates the role of *Faecalibacterium prausnitzii* in coronary artery disease (CAD) and its potential as an antiatherosclerotic microbe. Through metagenomic sequencing and untargeted metabolomics, the researchers identified *F. prausnitzii* as a significant biomarker associated with CAD incidence across various patient groups. In vitro and in vivo experiments further revealed that *F. prausnitzii* mitigates inflammation and exhibits antiatherosclerotic effects in ApoE−/− mice by reducing intestinal LPS synthesis and strengthening mechanical and mucosal barriers. These findings suggest that *F. prausnitzii* may serve as a promising therapeutic target for preventing CAD by inhibiting atherosclerosis.