title: Absence of intestinal microbiota increases ß-cyclodextrin stimulated reverse cholesterol transport.
abstract: Non-digestible oligosaccharides are used as prebiotics for perceived health benefits, among these modulating lipid metabolism. However, the mechanisms of action are incompletely understood. The present study characterized the impact of dietary ß-cyclodextrin (ßCD, 10%, w/w), a cyclic oligosaccharide, on sterol metabolism and reverse cholesterol transport (RCT) in conventional and also germ-free mice to establish dependency on metabolism by intestinal bacteria.
  
  
  
  In conventional ßCD-fed C57BL/6J wild-type mice plasma cholesterol decreased significantly (-40%, p < 0.05), largely within HDL, while fecal neutral sterol excretion increased (3-fold, p < 0.01) and fecal bile acid excretion was unchanged. Hepatic cholesterol levels and biliary cholesterol secretion were unaltered. Changes in cholesterol metabolism translated into increased macrophage-to-feces RCT in ßCD-administered mice (1.5-fold, p < 0.05). In germ-free C57BL/6J mice ßCD similarly lowered plasma cholesterol (-40%, p < 0.05). However, ßCD increased fecal neutral sterol excretion (7.5-fold, p < 0.01), bile acid excretion (2-fold, p < 0.05) and RCT (2.5-fold, p < 0.01) even more substantially in germ-free mice compared with the effect in conventional mice.
  
  
  
  In summary, this study demonstrates that ßCD lowers plasma cholesterol levels and increases fecal cholesterol excretion from a RCT-relevant pool. Intestinal bacteria decrease the impact of ßCD on RCT. These data suggest that dietary ßCD might have cardiovascular health benefits.
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Rima H
authors.initials: RH
authors.lastname: Mistry
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henkjan J
authors.initials: HJ
authors.lastname: Verkade
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Uwe J F
authors.initials: UJF
authors.lastname: Tietge
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000032:analysis; D001692:Biological Transport; D002784:Cholesterol / Q000097:blood* / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D000069196:Gastrointestinal Microbiome; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D056692:Prebiotics / Q000008:administration & dosage; D013261:Sterols / Q000032:analysis; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000097:blood*
chemical_list: D001647:Bile Acids and Salts; D056692:Prebiotics; D013261:Sterols; D047392:beta-Cyclodextrins; D002784:Cholesterol
keywords: Bile; Germ-free; Microbiota; Reverse cholesterol transport; ß-cyclodextrin