title: Gut Microbiota Modulation Attenuated the Hypolipidemic Effect of Simvastatin in High-Fat/Cholesterol-Diet Fed Mice.
abstract: The hypolipidemic effect of simvastatin varies greatly among patients. In the current study, we investigated the gut microbial-involved mechanisms underlying the different responses to simvastatin. Male C57BL/6J mice were divided into control (Con), high-fat/cholesterol diet (HFD), antibiotic (AB), simvastatin (SV) and antibiotic_simvastatin (AB_SV) groups, respectively. At the end of the experiment, serum samples were collected for lipids and metabolomic analysis, and liver tissues for histology, gene and protein expression analysis. The results showed that antibiotic treatment not only altered the composition of gut microbiota, but attenuated the hypolipidemic effect of SV. A total of 16 differential metabolites between SV and HFD groups were identified with metabolomics, while most of them showed no statistical differences between AB_SV and HFD groups, and similar changes were also observed in bile acids profile. The expressions of several genes and proteins involved in regulating bile acids synthesis were significantly reversed by SV, but not AB_SV in HFD fed mice. In summary, our current study indicated that the hypolipidemic effect of SV was correlated with the composition of the gut microbiota, and the attenuated hypolipidemic effect of SV by gut microbiota modulation was associated with a suppression of bile acids synthesis from cholesterol.
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, China.
authors.forename: Xuyun
authors.initials: X
authors.lastname: He
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, China.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: He
authors.affiliation: Laboratory Medicine of Southern Medical University Affiliated Fengxian Hospital , Shanghai 201499, China.
authors.forename: Can
authors.initials: C
authors.lastname: Liu
authors.affiliation: Laboratory Medicine of Southern Medical University Affiliated Fengxian Hospital , Shanghai 201499, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Feng
authors.affiliation: Center for Translational Medicine, and Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital , Shanghai 200233, China.|Cancer Epidemiology Program, University of Hawaii Cancer Center , Honolulu, Hawaii 96813, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Jia
authors.affiliation: Center for Chinese Medical Therapy and Systems Biology, Shanghai University of Traditional Chinese Medicine , Shanghai 201203, China.
authors.forename: Houkai
authors.identifier: 0000-0003-2846-7895
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001647:Bile Acids and Salts / Q000032:analysis / Q000378:metabolism; D002784:Cholesterol; D059305:Diet, High-Fat; D000069196:Gastrointestinal Microbiome / Q000187:drug effects; D000960:Hypolipidemic Agents / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019821:Simvastatin / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D000960:Hypolipidemic Agents; D002784:Cholesterol; D019821:Simvastatin
keywords: antibiotic; gut microbiota; hypolipidemic effect; metabolomics; simvastatin