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

Prasant K. Jena, Lili Sheng, Hui Xin Liu, Karen M. Kalanetra, Annie Mirsoian, William J Murphy, Samuel W. French, Viswanathan V Krishnan, David A. Mills, Yu-Jui Yvonne Wan

Research output: Contribution to journalArticle

25 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1800-1813
Number of pages14
JournalAmerican Journal of Pathology
Volume187
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Dysbiosis
Knockout Mice
Anti-Bacterial Agents
Inflammation
Liver
Proteobacteria
Polymyxin B
Lymphocytes
Bile Acids and Salts
Therapeutics
Lactococcus
Bacteroidetes
Neomycin
Neutrophil Infiltration
Microbiota
Metronidazole
Lactobacillus
Fatty Liver
Vancomycin
Ampicillin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Western Diet–Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment. / Jena, Prasant K.; Sheng, Lili; Liu, Hui Xin; Kalanetra, Karen M.; Mirsoian, Annie; Murphy, William J; French, Samuel W.; Krishnan, Viswanathan V; Mills, David A.; Wan, Yu-Jui Yvonne.

In: American Journal of Pathology, Vol. 187, No. 8, 01.08.2017, p. 1800-1813.

Research output: Contribution to journalArticle

Jena, Prasant K. ; Sheng, Lili ; Liu, Hui Xin ; Kalanetra, Karen M. ; Mirsoian, Annie ; Murphy, William J ; French, Samuel W. ; Krishnan, Viswanathan V ; Mills, David A. ; Wan, Yu-Jui Yvonne. / Western Diet–Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment. In: American Journal of Pathology. 2017 ; Vol. 187, No. 8. pp. 1800-1813.
@article{fa5fa2715ba140b285c3bc0c1ddec085,
title = "Western Diet–Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment",
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.",
author = "Jena, {Prasant K.} and Lili Sheng and Liu, {Hui Xin} and Kalanetra, {Karen M.} and Annie Mirsoian and Murphy, {William J} and French, {Samuel W.} and Krishnan, {Viswanathan V} and Mills, {David A.} and Wan, {Yu-Jui Yvonne}",
year = "2017",
month = "8",
day = "1",
doi = "10.1016/j.ajpath.2017.04.019",
language = "English (US)",
volume = "187",
pages = "1800--1813",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "8",

}

TY - JOUR

T1 - Western Diet–Induced Dysbiosis in Farnesoid X Receptor Knockout Mice Causes Persistent Hepatic Inflammation after Antibiotic Treatment

AU - Jena, Prasant K.

AU - Sheng, Lili

AU - Liu, Hui Xin

AU - Kalanetra, Karen M.

AU - Mirsoian, Annie

AU - Murphy, William J

AU - French, Samuel W.

AU - Krishnan, Viswanathan V

AU - Mills, David A.

AU - Wan, Yu-Jui Yvonne

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85023167727&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85023167727&partnerID=8YFLogxK

U2 - 10.1016/j.ajpath.2017.04.019

DO - 10.1016/j.ajpath.2017.04.019

M3 - Article

C2 - 28711154

AN - SCOPUS:85023167727

VL - 187

SP - 1800

EP - 1813

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 8

ER -