Abstract: Objective To explore the relationship between fecal metabolomics characteristics and the therapeutic effects of statins. Methods Fecal samples were collected from 60 patients with coronary heart disease undergoing statin therapy. Based on whether their low-density lipoprotein (LDL) level were below 1.9 mmol/L after treatment, the patients were divided into an effective treatment group and ineffective treatment group with 30 cases in each. Non-targeted metabolomics and targeted short-chain fatty acid sequencing were performed with the fecal samples and the sequencing results were analyzed. Results Principal Component Analysis (PCA) showed significant differences between the effective and ineffective treatment groups. Differential analysis identified 319 ions significantly different between the two groups in positive ion mode and negative ion mode. Enrichment analysis indicated that several pathways including taurine and hypotaurine metabolism, riboflavin metabolism, and fatty acid metabolism were enriched. Based on 113 diagnostic models, the top 10 models with the best predictive ability for treatment efficacy were selected, with Prilocaine, Glufosinate, and His-Gly-His showing the highest predictive capability across all models [area under the curve(AUC＞0.6)]. The level of Prilocaine and His-Gly-His was higher in effective treatment group while the level of Glufosinate was lower in the effective treatment group (P＜0.05). Additionally, short-chain fatty acid sequencing results showed that the level of Butyric acid and Propionic acid were significantly lower in the effective treatment group (P＜0.01). Butyric acid and Propionic acid were negatively correlated with Prilocaine and positively correlated with His-Gly-His. Conclusions The association between the efficacy of statins therapy and fecal metabolomics characteristics highlights the predictive value of changes in metabolite level such as Prilocaine, Glufosinate, and His-Gly-His which are potentially regulated by short-chain fatty acids.

Key words: coronary heart disease, statins, intestinal metabolites, short chain fatty acids