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  The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation

Schrumpf, E., Kummen, M., Valestrand, L., Greiner, T., Holm, K., Arulampalam, V., et al. (2016). The gut microbiota contributes to a mouse model of spontaneous bile duct inflammation. Journal of Hepatology, 66, 382-389. doi:10.1016/j.jhep.2016.09.020.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-3AF6-F Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002C-40E8-B
Genre: Journal Article


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Schrumpf, E., Author
Kummen, M., Author
Valestrand, L., Author
Greiner, T.U., Author
Holm, K., Author
Arulampalam, V., Author
Reims, H.M., Author
Baines, J.1, Author              
Bäckhed, F., Author
Karlsen, T.H., Author
Blumberg, R.S., Author
Hov, J.R., Author
Melum, E., Author
1Guest Group Evolutionary Genomics, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445638              


Free keywords: Germ free; Microbiota; NOD.c3c4; PBC; PSC; Mice, inbred NOD; Inflammation; Mucous membrane; Gastrointestinal microbiome; Liver; Antibacterial agents
 Abstract: Background Aims: A strong association between human inflammatory biliary diseases and gut inflammation has led to the hypothesis that gut microbes and lymphocytes activated in the intestine play a role in biliary inflammation. The NOD.c3c4 mouse model develops spontaneous biliary inflammation in extra- and intrahepatic bile ducts. We aimed to clarify the role of the gut microbiota in the biliary disease of NOD.c3c4 mice. Methods: We sampled cecal content and mucosa from conventionally raised (CONV-R) NOD.c3c4 and NOD control mice, extracted DNA and performed 16S rRNA sequencing. NOD.c3c4 mice were rederived into a germ free (GF) facility and compared with CONV-R NOD.c3c4 mice. NOD.c3c4 mice were also co-housed with NOD mice and received antibiotics from weaning. Results: The gut microbial profiles of mice with and without biliary disease were different both before and after rederivation (unweighted UniFrac-distance). GF NOD.c3c4 mice had less distended extra-hepatic bile ducts than CONV-R NOD.c3c4 mice, while antibiotic treated mice showed reduction of biliary infarcts. GF animals also showed a reduction in liver weight compared with CONV-R NOD.c3c4 mice, and this was also observed in antibiotic treated NOD.c3c4 mice. Co-housing of NOD and NOD.c3c4 mice indicated that the biliary phenotype was neither transmissible nor treatable by co-housing with healthy mice. Conclusions: NOD.c3c4 and NOD control mice show marked differences in the gut microbiota. GF NOD.c3c4 mice develop a milder biliary affection compared with conventionally raised NOD.c3c4 mice. Our findings suggest that the intestinal microbiota contributes to disease in this murine model of biliary inflammation. Lay summary: Mice with liver disease have a gut microflora (microbiota) that differs substantially from normal mice. In a normal environment, these mice spontaneously develop disease in their bile ducts. However, when these mice, are raised in an environment devoid of bacteria, the disease in the bile ducts diminishes. Overall this clearly indicates that the bacteria in the gut (the gut microbiota) influences the liver disease in these mice. © 2016 European Association for the Study of the Liver.


Language(s): eng - English
 Dates: 2015-11-252016-09-292016-10-052016
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.jhep.2016.09.020
BibTex Citekey: Schrumpf2016
 Degree: -



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Title: Journal of Hepatology
  Other : J. Hepatol.
Source Genre: Journal
Publ. Info: Amsterdam : Elsevier
Pages: - Volume / Issue: 66 Sequence Number: - Start / End Page: 382 - 389 Identifier: ISSN: 0168-8278
CoNE: https://pure.mpg.de/cone/journals/resource/954925485712