title: Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes.
abstract: OBJECTIVE
  We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol-lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect.
  
  
  METHODS
  Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks.
  
  
  RESULTS
  C57BL/6 NCrl mice responded to oat bran with 19 ± 1 % (P < 0.001) lower plasma cholesterol, 40 ± 5% (P < 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indicated improved glycemic control by oat bran in C57BL/6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower numbers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl.
  
  
  CONCLUSIONS
  Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol-lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol.
authors.affiliation: Department of Experimental Medical Science, Lund University, BMC D12, 221 84, Lund, Sweden, Kristina_E.Andersson@med.lu.se.
authors.forename: Kristina E
authors.initials: KE
authors.lastname: Andersson
authors.forename: Ulrika
authors.initials: U
authors.lastname: Axling
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.forename: Karl
authors.initials: K
authors.lastname: Swärd
authors.forename: Siv
authors.initials: S
authors.lastname: Ahrné
authors.forename: Göran
authors.initials: G
authors.lastname: Molin
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
authors.forename: Per
authors.initials: P
authors.lastname: Hellstrand
mesh_terms: D000818:Animals; D018554:Avena / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001835:Body Weight; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D004036:Diet, Atherogenic; D004043:Dietary Fiber / Q000008:administration & dosage; D005243:Feces / Q000737:chemistry; D005260:Female; D019270:Fructosamine / Q000097:blood; D005951:Glucose Tolerance Test; D007408:Intestinal Absorption / Q000502:physiology; D007422:Intestines / Q000382:microbiology; D050356:Lipid Metabolism; D008099:Liver / Q000201:enzymology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D015999:Multivariate Analysis; D025341:Principal Component Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013253:Steroid 12-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D001647:Bile Acids and Salts; D002788:Cholesterol Esters; D004043:Dietary Fiber; D012333:RNA, Messenger; D019270:Fructosamine; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; C502772:Cyp7a1 protein, mouse; D013253:Steroid 12-alpha-Hydroxylase