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Am J Pathol. 2017 Aug;187(8):1800-1813. doi: 10.1016/j.ajpath.2017.04.019. Epub 2017 Jul 12.

Western Diet-Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment.

Author information

1
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California.
2
Department of Food Science and Technology, University of California, Davis, Sacramento, California; Department of Viticulture and Enology, University of California, Davis, Sacramento, California.
3
Department of Dermatology, University of California, Davis, Sacramento, California.
4
Department of Pathology, Harbor UCLA Medical Center, Torrance, California.
5
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California; Department of Chemistry, College of Science and Mathematics, Fresno State University, Fresno, California.
6
Department of Medical Pathology and Laboratory Medicine, University of California, Davis, Sacramento, California. Electronic address: yjywan@ucdavis.edu.

Erratum in

Abstract

Patients who have liver cirrhosis and liver cancer also have reduced farnesoid X receptor (FXR). The current study analyzes the effect of diet through microbiota that affect hepatic inflammation in FXR knockout (KO) mice. Wild-type and FXR KO mice were on a control (CD) or Western diet (WD) for 10 months. In addition, both CD- and WD-fed FXR KO male mice, which had hepatic lymphocyte and neutrophil infiltration, were treated by vancomycin, polymyxin B, and Abx (ampicillin, neomycin, metronidazole, and vancomycin). Mice were subjected to morphological analysis as well as gut microbiota and bile acid profiling. Male WD-fed FXR KO mice had the most severe steatohepatitis. FXR KO also had reduced Firmicutes and increased Proteobacteria, which could be reversed by Abx. In addition, Abx eliminated hepatic neutrophils and lymphocytes in CD-fed, but not WD-fed, FXR KO mice. Proteobacteria and Bacteroidetes persisted in WD-fed FXR KO mice even after Abx treatment. Only polymyxin B could reduce hepatic lymphocytes in WD-fed FXR KO mice. The reduced hepatic inflammation by antibiotics was accompanied by decreased free and conjugated secondary bile acids as well as changes in gut microbiota. Our data revealed that Lactococcus, Lactobacillus, and Coprococcus protect the liver from inflammation.

PMID:
28711154
PMCID:
PMC5530909
DOI:
10.1016/j.ajpath.2017.04.019
[Indexed for MEDLINE]
Free PMC Article

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