Huimin Li,1,2,* Shue Wang,3,* Shuai Wang,4 Hai Yu,1 Wenhao Yu,5,6 Xiaomin Ma,3 Xiaodong He1,6 1Department of Physical and Chemical Inspection, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2National Human Genetic Resources Center; National Research Institute for Health and Family Planning; Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 3Preventive Medicine Experimental Teaching Center, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 4Department of Toxicology and Nutrition, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 5Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 6Institute for Medical Dataology, Shandong University, National Institute of Health Data Science of China, Jinan, Shandong, 250012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong He, Tel/Fax +86 531 88382554, Email xiaodong.he@sdu.edu.cnPurpose: The prevalence of hyperlipidemia and related illnesses is on its rise, and atorvastatin is the frequently used hypolipidemic agent. However, there is still uncertainty about the mechanisms, especially the relationship between the lipid-lowering effect, intestinal microbiome, and metabolic profiles. We aim to intensively explain the mechanism of the hypolipidemic effect of atorvastatin through multi-omics perspective of intestinal microbiome and metabolomics.Methods: Multi-omics methods play an increasingly important role in the analysis of intestinal triggers and evaluation of metabolic disorders such as obesity, hyperlipidemia, and diabetes. Therefore, we were prompted to explore intestinal triggers, underlying biomarkers, and potential intervention targets of atorvastatin in the treatment of dyslipidemia through multi-omics. To achieve this, SPF Wistar rats were fed a high-fat diet or normal diet for 8 weeks. Atorvastatin was then administered to high-fat diet-fed rats.Results: By altering intestinal microbiome, a high-fat diet can affect feces and plasma metabolic profiles. Treatment with atorvastatin possibly increases the abundance of Bacteroides, thereby improving “propanoate metabolism” and “glycine, serine and threonine metabolism” in feces and plasma, and contributing to blood lipid reduction.Conclusion: Our study elucidated the intestinal triggers and metabolites of high-fat diet-induced dyslipidemia from the perspective of intestinal microbiome and metabolomics. It equally identified potential intervention targets of atorvastatin. This further explains the mechanism of the hypolipidemic effect of atorvastatin from a multi-omics perspective.Keywords: hyperlipidemia, 16S rRNA sequencing, intestinal microbiome, metabolomics, atorvastatin calcium trihydrate
