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

doi:10.1016/j.jcf.2014.12.010

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

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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 language	English
Pages (from-to)	440-446
Number of pages	7
Journal	Journal of Cystic Fibrosis
Volume	14
Issue number	4
DOIs	https://doi.org/10.1016/j.jcf.2014.12.010
Publication status	Published - Jul-2015

Keywords

Cystic fibrosis
Liver disease
Bile salts
Ursocholic acid
Mice model
Intestinal bacterial microflora
CFTR
LIVER-DISEASE
ACID MALABSORPTION
FAT-ABSORPTION
RAPID METHOD
DUCT INJURY
MICE
EXTRACTION
FLOW

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10.1016/j.jcf.2014.12.010

Altered intestinal bile salt biotransformation in a cystic fibrosisFinal publisher's version, 515 KBLicence: Elsevier

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@article{cf7de20303e744a1ab7e613d444001b5,

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

abstract = "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.",

keywords = "Cystic fibrosis, Liver disease, Bile salts, Ursocholic acid, Mice model, Intestinal bacterial microflora, CFTR, LIVER-DISEASE, ACID MALABSORPTION, FAT-ABSORPTION, RAPID METHOD, DUCT INJURY, MICE, EXTRACTION, FLOW",

author = "Bodewes, \{Frank A. J. A.\} and \{van der Wulp\}, \{Mariette Y. M.\} and Satti Beharry and Marcela Doktorova and Rick Havinga and Renze Boverhof and Phillips, \{M. James\} and Durie, \{Peter R.\} and Verkade, \{Henkjan J.\}",

note = "Copyright {\textcopyright} 2014. Published by Elsevier B.V.",

year = "2015",

month = jul,

doi = "10.1016/j.jcf.2014.12.010",

language = "English",

volume = "14",

pages = "440--446",

journal = "Journal of Cystic Fibrosis",

issn = "1569-1993",

publisher = "ELSEVIER SCIENCE BV",

number = "4",

}

TY - JOUR

T1 - Altered intestinal bile salt biotransformation in a cystic fibrosis (Cftr(-/-)) mouse model with hepato-biliary pathology

AU - Bodewes, Frank A. J. A.

AU - van der Wulp, Mariette Y. M.

AU - Beharry, Satti

AU - Doktorova, Marcela

AU - Havinga, Rick

AU - Boverhof, Renze

AU - Phillips, M. James

AU - Durie, Peter R.

AU - Verkade, Henkjan J.

PY - 2015/7

Y1 - 2015/7

N2 - 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.

AB - 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.

KW - Cystic fibrosis

KW - Liver disease

KW - Bile salts

KW - Ursocholic acid

KW - Mice model

KW - Intestinal bacterial microflora

KW - CFTR

KW - LIVER-DISEASE

KW - ACID MALABSORPTION

KW - FAT-ABSORPTION

KW - RAPID METHOD

KW - DUCT INJURY

KW - MICE

KW - EXTRACTION

KW - FLOW

U2 - 10.1016/j.jcf.2014.12.010

DO - 10.1016/j.jcf.2014.12.010

M3 - Article

C2 - 25633479

SN - 1569-1993

VL - 14

SP - 440

EP - 446

JO - Journal of Cystic Fibrosis

JF - Journal of Cystic Fibrosis

IS - 4

ER -

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

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