title: Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr-/-) mouse model with hepato-biliary pathology.
abstract: BACKGROUND
  Cftr(-/-tm1Unc) mice develop progressive hepato-biliary pathology. We hypothesize that this liver pathology is related to alterations in biliary bile hydrophobicity and bile salt metabolism in Cftr(-/-tm1Unc) mice.
  
  
  METHODS
  We determined bile production, biliary and fecal bile salt- and lipid compositions and fecal bacterial composition of C57BL/6J Cftr(-/-tm1Unc) and control mice.
  
  
  RESULTS
  We found no differences between the total biliary bile salt or lipid concentrations of Cftr(-/-) and controls. Compared to controls, Cftr(-/-) mice had a ~30% higher bile production and a low bile hydrophobicity, related to a ~7 fold higher concentration of the choleretic and hydrophilic bile salt ursocholate. These findings coexisted with a significantly smaller quantity of fecal Bacteroides bacteria.
  
  
  CONCLUSIONS
  Liver pathology in Cftr(-/-tm1Unc) is not related to increased bile hydrophobicity. Cftr(-/-) mice do however display a biliary phenotype characterized by increased bile production and decreased biliary hydrophobicity. Our findings suggest Cftr dependent, alterations in intestinal bacterial biotransformation of bile salts.
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands. Electronic address: f.a.j.a.bodewes@umcg.nl.
authors: Frank A J A
authors: FA
authors: Bodewes
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors: Mariëtte Y M
authors: MY
authors: van der Wulp
authors: Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada.
authors: Satti
authors: S
authors: Beharry
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors: Marcela
authors: M
authors: Doktorova
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors: Rick
authors: R
authors: Havinga
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors: Renze
authors: R
authors: Boverhof
authors: Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada.
authors: M
authors: M
authors: James Phillips
authors: Gastroenterology, Hepatology and Nutrition, The Hospital for Sick Children, 555 University Ave, Toronto, ON M5G 1X8, Canada.
authors: Peter R
authors: PR
authors: Durie
authors: Pediatric Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, PO Box 30001, 9700 RB Groningen, The Netherlands.
authors: Henkjan J
authors: HJ
authors: Verkade
mesh_terms: D000818:Animals; D001646:Bile / Q000502:physiology*; D001647:Bile Acids and Salts / Q000378:metabolism*; D001652:Bile Ducts / Q000473:pathology*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D004195:Disease Models, Animal; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D057927:Hydrophobic and Hydrophilic Interactions; D008099:Liver / Q000473:pathology*; D008297:Male; D051379:Mice; D020297:Mice, Congenic; D008810:Mice, Inbred C57BL
chemical_list: D001647:Bile Acids and Salts; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Bile salts; CFTR; Cystic fibrosis; Intestinal bacterial microflora; Liver disease; Mice model; Ursocholic acid