title: Reverse Cholesterol Transport Is Increased in Germ-Free Mice-Brief Report.
abstract: OBJECTIVE
  The intestinal microbiota is emerging as a clinically relevant modulator of atherosclerotic risk. Reverse cholesterol transport (RCT) is an atheroprotective metabolic pathway. How the microbiota impacts RCT has not been investigated. Therefore, the aim of this study was to characterize (cholesterol) metabolism and RCT in germ-free mice compared with conventional mice.
  
  
  RESULTS
  In chow-fed germ-free mice, plasma cholesterol was unchanged, whereas liver cholesterol content was higher (1.5-fold;P<0.05) than in conventional controls. Biliary secretion of cholesterol (2-fold;P<0.001) and bile acids (3-fold;P<0.001) was substantially increased in the germ-free model, whereas fecal neutral sterol excretion was unaltered, and fecal bile acid excretion was decreased (P<0.01). However, fecal bile acid profiles of germ-free mice were dominated by the presence of β-muricholic acid (P<0.001), pointing toward a higher contribution of the alternative acidic pathway to total bile acid synthesis in these mice. As expected, secondary bile acids were absent in the germ-free model. In vivo macrophage-to-feces RCT was increased >2-fold (P<0.01) in the absence of intestinal bacteria.
  
  
  CONCLUSIONS
  These data demonstrate that the absence of the intestinal microbiota stimulates RCT >2-fold. Thereby, our results support the importance of intestinal bacteria for metabolic regulation and indicate that specific targeting of the microbiota bears therapeutic potential to prevent and treat cardiovascular disease.
authors.affiliation: From the Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Rima H
authors.initials: RH
authors.lastname: Mistry
authors.affiliation: From the Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, The Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: From the Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, The Netherlands. u_tietge@yahoo.com.
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood*; D005243:Feces / Q000737:chemistry; D000069196:Gastrointestinal Microbiome; D015971:Gene Expression Regulation, Enzymologic; D005856:Germ-Free Life; D007422:Intestines / Q000382:microbiology*; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D015854:Up-Regulation
chemical_list: D001647:Bile Acids and Salts; D002784:Cholesterol
keywords: bacteria; cholesterol; liver; microbiota; sterols