ArticleClinical science (London, England : 1979)2023
Absence of gut microbiota reduces neonatal survival and exacerbates liver disease in Cyp2c70-deficient mice with a human-like bile acid composition.
Article in Clinical science (London, England : 1979), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Article
- Human Microbiota-Associated Pig Models for Translational Microbiome Research: A Scoping Review.International journal of molecular sciences · 2026Article
- Sucrose-preferring gut microbes prevent host obesity by producing exopolysaccharides.Nature communications · 2025Article
- Human microbiota-associated animal models: a review.Frontiers in cellular and infection microbiology · 2025Review
- Importance of the gut microbiota in mice with a 'humanized' bile acid pool.Clinical science (London, England : 1979) · 2024Article
- Gut microbiota depletion aggravates bile acid-induced liver pathology in mice with a human-like bile acid composition.Clinical science (London, England : 1979) · 2023Article
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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