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 sal...
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| Veröffentlicht in: | Journal of cystic fibrosis 2015-07, Vol.14 (4), p.440-446 |
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| creator | Bodewes, Frank A.J.A van der Wulp, Mariëtte Y.M Beharry, Satti Doktorova, Marcela Havinga, Rick Boverhof, Renze James Phillips, M Durie, Peter R Verkade, Henkjan J |
| description | 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/6 J 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. |
| doi_str_mv | 10.1016/j.jcf.2014.12.010 |
| format | Article |
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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 −/− 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.</description><identifier>ISSN: 1569-1993</identifier><identifier>EISSN: 1873-5010</identifier><identifier>DOI: 10.1016/j.jcf.2014.12.010</identifier><identifier>PMID: 25633479</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>Animals ; Bile - physiology ; Bile Acids and Salts - metabolism ; Bile Ducts - pathology ; Bile salts ; CFTR ; Cystic fibrosis ; Cystic Fibrosis - metabolism ; Cystic Fibrosis - pathology ; Cystic Fibrosis Transmembrane Conductance Regulator ; Disease Models, Animal ; Feces - chemistry ; Feces - microbiology ; Female ; Hydrophobic and Hydrophilic Interactions ; Intestinal bacterial microflora ; Liver - pathology ; Liver disease ; Male ; Mice ; Mice model ; Mice, Congenic ; Mice, Inbred C57BL ; Pulmonary/Respiratory ; Ursocholic acid</subject><ispartof>Journal of cystic fibrosis, 2015-07, Vol.14 (4), p.440-446</ispartof><rights>2014</rights><rights>Copyright © 2014. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c521t-337a06e42aee0ec64c6c267eebd6bada667cb853db55879e65c19ee5527eabc53</citedby><cites>FETCH-LOGICAL-c521t-337a06e42aee0ec64c6c267eebd6bada667cb853db55879e65c19ee5527eabc53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jcf.2014.12.010$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25633479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bodewes, Frank A.J.A</creatorcontrib><creatorcontrib>van der Wulp, Mariëtte Y.M</creatorcontrib><creatorcontrib>Beharry, Satti</creatorcontrib><creatorcontrib>Doktorova, Marcela</creatorcontrib><creatorcontrib>Havinga, Rick</creatorcontrib><creatorcontrib>Boverhof, Renze</creatorcontrib><creatorcontrib>James Phillips, M</creatorcontrib><creatorcontrib>Durie, Peter R</creatorcontrib><creatorcontrib>Verkade, Henkjan J</creatorcontrib><title>Altered intestinal bile salt biotransformation in a cystic fibrosis ( Cftr−/− ) mouse model with hepato-biliary pathology</title><title>Journal of cystic fibrosis</title><addtitle>J Cyst Fibros</addtitle><description>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/6 J 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.</description><subject>Animals</subject><subject>Bile - physiology</subject><subject>Bile Acids and Salts - metabolism</subject><subject>Bile Ducts - pathology</subject><subject>Bile salts</subject><subject>CFTR</subject><subject>Cystic fibrosis</subject><subject>Cystic Fibrosis - metabolism</subject><subject>Cystic Fibrosis - pathology</subject><subject>Cystic Fibrosis Transmembrane Conductance Regulator</subject><subject>Disease Models, Animal</subject><subject>Feces - chemistry</subject><subject>Feces - microbiology</subject><subject>Female</subject><subject>Hydrophobic and Hydrophilic Interactions</subject><subject>Intestinal bacterial microflora</subject><subject>Liver - pathology</subject><subject>Liver disease</subject><subject>Male</subject><subject>Mice</subject><subject>Mice model</subject><subject>Mice, Congenic</subject><subject>Mice, Inbred C57BL</subject><subject>Pulmonary/Respiratory</subject><subject>Ursocholic acid</subject><issn>1569-1993</issn><issn>1873-5010</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9UT2P1DAUjBCIOw5-AA1yeRTJ-SO2EyEhnVZ8SSdRALXlOC-sgxMvtvfQFvTU_ER-CW-1BwUFhe2xNDN6M6-qnjLaMMrU1dzMbmo4ZW3DeEMZvVeds06LWiK-j1iqvmZ9L86qRznPlDJNdfewOuNSCdHq_rz6fh0KJBiJXwvk4lcbyOADkGxDQRRLsmueYlps8XFFGrHEHZDpyOSHFLPP5JJsppJ-_fh5hYc8J0vcZ8B7hEC--bIlW9jZEms09jYdCH62McTPh8fVg8mGDE_u3ovq0-tXHzdv65v3b95trm9qJzkrtRDaUgUttwAUnGqdclxpgGFUgx2tUtoNnRTjIGWne1DSsR5ASq7BDk6Ki-ry5LtL8esec5rFZwch2BVwVsNUz3nPW9ohlZ2oDrPlBJPZJb_g1IZRc2zdzAZbN8fWDeMGm0bNszv7_bDA-Ffxp2YkvDgRAEPeekgmOw-rg9EncMWM0f_X_uU_ahf86p0NX-AAeY77hGvDFCajwHw4rv24ddZSKqiW4jcZd6sv</recordid><startdate>20150701</startdate><enddate>20150701</enddate><creator>Bodewes, Frank A.J.A</creator><creator>van der Wulp, Mariëtte Y.M</creator><creator>Beharry, Satti</creator><creator>Doktorova, Marcela</creator><creator>Havinga, Rick</creator><creator>Boverhof, Renze</creator><creator>James Phillips, M</creator><creator>Durie, Peter R</creator><creator>Verkade, Henkjan J</creator><general>Elsevier B.V</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20150701</creationdate><title>Altered intestinal bile salt biotransformation in a cystic fibrosis ( Cftr−/− ) mouse model with hepato-biliary pathology</title><author>Bodewes, Frank A.J.A ; van der Wulp, Mariëtte Y.M ; Beharry, Satti ; Doktorova, Marcela ; Havinga, Rick ; Boverhof, Renze ; James Phillips, M ; Durie, Peter R ; Verkade, Henkjan J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c521t-337a06e42aee0ec64c6c267eebd6bada667cb853db55879e65c19ee5527eabc53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Bile - physiology</topic><topic>Bile Acids and Salts - metabolism</topic><topic>Bile Ducts - pathology</topic><topic>Bile salts</topic><topic>CFTR</topic><topic>Cystic fibrosis</topic><topic>Cystic Fibrosis - metabolism</topic><topic>Cystic Fibrosis - pathology</topic><topic>Cystic Fibrosis Transmembrane Conductance Regulator</topic><topic>Disease Models, Animal</topic><topic>Feces - chemistry</topic><topic>Feces - microbiology</topic><topic>Female</topic><topic>Hydrophobic and Hydrophilic Interactions</topic><topic>Intestinal bacterial microflora</topic><topic>Liver - pathology</topic><topic>Liver disease</topic><topic>Male</topic><topic>Mice</topic><topic>Mice model</topic><topic>Mice, Congenic</topic><topic>Mice, Inbred C57BL</topic><topic>Pulmonary/Respiratory</topic><topic>Ursocholic acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bodewes, Frank A.J.A</creatorcontrib><creatorcontrib>van der Wulp, Mariëtte Y.M</creatorcontrib><creatorcontrib>Beharry, Satti</creatorcontrib><creatorcontrib>Doktorova, Marcela</creatorcontrib><creatorcontrib>Havinga, Rick</creatorcontrib><creatorcontrib>Boverhof, Renze</creatorcontrib><creatorcontrib>James Phillips, M</creatorcontrib><creatorcontrib>Durie, Peter R</creatorcontrib><creatorcontrib>Verkade, Henkjan J</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of cystic fibrosis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bodewes, Frank A.J.A</au><au>van der Wulp, Mariëtte Y.M</au><au>Beharry, Satti</au><au>Doktorova, Marcela</au><au>Havinga, Rick</au><au>Boverhof, Renze</au><au>James Phillips, M</au><au>Durie, Peter R</au><au>Verkade, Henkjan J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Altered intestinal bile salt biotransformation in a cystic fibrosis ( Cftr−/− ) mouse model with hepato-biliary pathology</atitle><jtitle>Journal of cystic fibrosis</jtitle><addtitle>J Cyst Fibros</addtitle><date>2015-07-01</date><risdate>2015</risdate><volume>14</volume><issue>4</issue><spage>440</spage><epage>446</epage><pages>440-446</pages><issn>1569-1993</issn><eissn>1873-5010</eissn><abstract>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/6 J 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.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>25633479</pmid><doi>10.1016/j.jcf.2014.12.010</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bile - physiology Bile Acids and Salts - metabolism Bile Ducts - pathology Bile salts CFTR Cystic fibrosis Cystic Fibrosis - metabolism Cystic Fibrosis - pathology Cystic Fibrosis Transmembrane Conductance Regulator Disease Models, Animal Feces - chemistry Feces - microbiology Female Hydrophobic and Hydrophilic Interactions Intestinal bacterial microflora Liver - pathology Liver disease Male Mice Mice model Mice, Congenic Mice, Inbred C57BL Pulmonary/Respiratory Ursocholic acid |
| title | Altered intestinal bile salt biotransformation in a cystic fibrosis ( Cftr−/− ) mouse model with hepato-biliary pathology |
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