title: Gut microbiota metabolism of anthocyanin promotes reverse cholesterol transport in mice via repressing miRNA-10b.
abstract: BACKGROUND
  We and others have demonstrated that anthocyanins have antiatherogenic capability. Because intact anthocyanins are absorbed very poorly, the low level of circulating parent anthocyanins may not fully account for their beneficial effect. We found recently that protocatechuic acid (PCA), a metabolite of cyanidin-3 to 0-β-glucoside (Cy-3-G), has a remarkable antiatherogenic effect.
  
  
  OBJECTIVE
  To investigate whether mouse gut microbiota metabolizes Cy-3-G into PCA and to determine whether and how PCA contributes to the antiatherogenic potency of its precursor, Cy-3-G.
  
  
  RESULTS
  PCA was determined as a gut microbiota metabolite of Cy-3-G in ApoE(-/-) mice, verified by the utilization of antibiotics to eliminate gut microbiota and further microbiota acquisition. PCA but not Cy-3-G at physiologically reachable concentrations promoted cholesterol efflux from macrophages and macrophage ABCA1 and ABCG1 expression. By conducting a miRNA microarray screening, we revealed that expression of miRNA-10b in macrophages can be reduced by PCA. Functional analyses demonstrated that miRNA-10b directly represses ABCA1 and ABCG1 and negatively regulates cholesterol efflux from murine- and human-derived macrophages. Further in vitro and ex vivo analyses verified that PCA accelerates macrophage cholesterol efflux, correlating with the regulation of miRNA-10b-ABCA1/ABCG1 cascade, whereas Cy-3-G consumption promoted macrophage RCT and regressed atherosclerotic lesion in a gut microbiotaendependent manner.
  
  
  CONCLUSIONS
  PCA, as the gut microbiota metabolite of Cy-3-G, exerts the antiatherogenic effect partially through this newly defined miRNA-10b-ABCA1/ABCG1-cholesterol efflux signaling cascade. Thus, gut microbiota is a potential novel target for atherosclerosis prevention and treatment.
authors: Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, PR China.
authors: Dongliang
authors: D
authors: Wang
authors: Min
authors: M
authors: Xia
authors: Xiao
authors: X
authors: Yan
authors: Dan
authors: D
authors: Li
authors: Lei
authors: L
authors: Wang
authors: Yuxuan
authors: Y
authors: Xu
authors: Tianru
authors: T
authors: Jin
authors: Wenhua
authors: W
authors: Ling
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000818:Animals; D000872:Anthocyanins / Q000378:metabolism / Q000494:pharmacology*; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D005960:Glucosides / Q000378:metabolism / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D062385:Hydroxybenzoates / Q000378:metabolism; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology; D007422:Intestines / Q000382:microbiology; D008074:Lipoproteins / Q000235:genetics; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D054892:Metagenome / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D035683:MicroRNAs / Q000378:metabolism*
chemical_list: C577836:ABCA1 protein, human; C487540:ABCG1 protein, mouse; D064286:ATP Binding Cassette Transporter 1; D000070998:ATP Binding Cassette Transporter, Subfamily G, Member 1; D018528:ATP-Binding Cassette Transporters; D000872:Anthocyanins; D001057:Apolipoproteins E; D005960:Glucosides; D062385:Hydroxybenzoates; D008074:Lipoproteins; C569259:MIRN10 microRNA, mouse; D035683:MicroRNAs; C462279:cyanidin-3-O-beta-glucopyranoside; C009091:protocatechuic acid; D002784:Cholesterol