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• W4382632031 abstract "Abstract Mice with deletion of Cyp2c70 have a human-like bile acid composition, display age- and sex-dependent signs of hepatobiliary disease and can be used as a model to study interactions between bile acids and the gut microbiota in cholestatic liver disease. In the present study, we rederived Cyp2c70−/− mice as germ-free (GF) and colonized them with a human or a mouse microbiota to investigate whether the presence of a microbiota can be protective in cholangiopathic liver disease associated with Cyp2c70-deficiency. GF Cyp2c70−/− mice showed reduced neonatal survival, liver fibrosis, and distinct cholangiocyte proliferation. Colonization of germ-free breeding pairs with a human or a mouse microbiota normalized neonatal survival of the offspring, and particularly colonization with mouse microbiota from a conventionally raised mouse improved the liver phenotype at 6–10 weeks of age. The improved liver phenotype in conventionalized (CD) Cyp2c70−/− mice was associated with increased levels of tauro-ursodeoxycholic acid (TUDCA) and UDCA, resulting in a more hydrophilic bile acid profile compared with GF and humanized Cyp2c70−/− mice. The hydrophobicity index of biliary bile acids of CD Cyp2c70−/− mice was associated with changes in gut microbiota, liver weight, liver transaminases, and liver fibrosis. Hence, our results indicate that neonatal survival of Cyp2c70−/− mice seems to depend on the establishment of a gut microbiota at birth, and the improved liver phenotype in CD Cyp2c70−/− mice may be mediated by a larger proportion of TUDCA/UDCA in the circulating bile acid pool and/or by the presence of specific bacteria." @default.
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• W4382632031 date "2023-07-01" @default.
• W4382632031 modified "2023-10-17" @default.
• W4382632031 title "Absence of gut microbiota reduces neonatal survival and exacerbates liver disease in <i>Cyp2c70</i>-deficient mice with a human-like bile acid composition" @default.
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• W4382632031 doi "https://doi.org/10.1042/cs20230413" @default.
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