[Objective] To explore the potential mechanism by which Prevotella copri promotes atherosclerosis (AS) from the perspective of host-gut microbiota-metabolism. [Methods] ApoE^-/- mice were randomized into four groups (n=8): control group (Chow group, fed with a normal diet), model group (AS group, fed with a high-fat diet), low-concentration P. copri group (P. copri-low group, administrated with P. copri at 10⁹ CFU/mL by oral gavage daily from the first day of feeding with the high-fat diet), and high-concentration P. copri group (P. copri-high group, administrated with P. copri at 10¹¹ CFU/mL by oral gavage daily from the first day of feeding with the high-fat diet). The body weight was measured and recorded weekly to evaluate the weight gain trend. After 5 weeks, oil red O staining was employed to evaluate the aortic plaque area, and enzyme-linked immunosorbent assay (ELISA) was employed to measure lipid levels, on the basis of which the impact of P. copri on AS progression was assessed. Additionally, qPCR was used to detect the abundance of P. copri in the gut, and untargeted metabolomics was employed to analyze the metabolite changes in the feces of mice. [Results] Compared with the Chow group, the AS group showed increases in the body weight, aortic plaque area, and plasma levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TG) and a decline in the high-density lipoprotein cholesterol (HDL-C) level. The abundance of P. copri in the gut showed no significant difference between the P. copri-low group and the P. copri-high group, indicating that P. copri successfully colonized the gut in both groups. Based on this, the P. copri-low group was selected as the standard concentration group (P. copri group) for further analysis. Compared with the AS group, P. copri colonization in the gut significantly increased the body weight and aortic plaque area and exacerbated dyslipidemia. Metabolomic analysis revealed that P. copri transplantation led to significant increases in the content of several metabolites, including Cer(d18:1/18:1(9Z)), N-palmitoylsphingosine, genistein, adenine, and linoleic acid. KEGG pathway enrichment analysis further indicated that P. copri might contribute to the development and progression of AS through key pathways such as the regulation of ABC transporters, bile acid metabolism, and neuroactive ligand-receptor interactions. [Conclusion] P. copri may exacerbate inflammation and lipid metabolism imbalance by regulating sphingolipid signaling, purine metabolism, and linoleic acid metabolism, thereby promoting the progression of AS.