Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr(-/-)) mouse model with hepato-biliary pathology

Frank A. J. A. Bodewes*, Mariette Y. M. van der Wulp, Satti Beharry, Marcela Doktorova, Rick Havinga, Renze Boverhof, M. James Phillips, Peter R. Durie, Henkjan J. Verkade

*Corresponding author for this work

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Background: Cftr(-/-tm1UC) 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/6 J Cftr(-/-1Unc) and control mice.

Results: We found no differences between the total biliary bile salt or lipid concentrations of Cfir(-/-) and controls. Compared to controls, Cftr(-/-) mice had a similar to 30% higher bile production and a low bile hydrophobicity, related to a similar to 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. (C) 2014 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.

Original languageEnglish
Pages (from-to)440-446
Number of pages7
JournalJournal of Cystic Fibrosis
Issue number4
Publication statusPublished - Jul-2015


  • Cystic fibrosis
  • Liver disease
  • Bile salts
  • Ursocholic acid
  • Mice model
  • Intestinal bacterial microflora
  • CFTR
  • MICE
  • FLOW

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