Nonalcoholic fatty liver disease is exacerbated in high-fat diet-fed gnotobiotic mice by colonization with the gut microbiota from patients with nonalcoholic steatohepatitis

Chien Chao Chiu, Yung Hao Ching, Yen Peng Li, Ju Yun Liu, Yen Te Huang, Yi Wen Huang, Sien Sing Yang, Wen Ching Huang, Hsiao Li Chuang

Research output: Contribution to journalArticlepeer-review

122 Citations (Scopus)

Abstract

Nonalcoholic fatty liver disease (NAFLD) is a serious liver disorder associated with the accumulation of fat and inflammation. The objective of this study was to determine the gut microbiota composition that might influence the progression of NAFLD. Germ-free mice were inoculated with feces from patients with nonalcoholic steatohepatitis (NASH) or from healthy persons (HL) and then fed a standard diet (STD) or high-fat diet (HFD). We found that the epididymal fat weight, hepatic steatosis, multifocal necrosis, and inflammatory cell infiltration significantly increased in the NASH-HFD group. These findings were consistent with markedly elevated serum levels of alanine transaminase, aspartate transaminase, endotoxin, interleukin 6 (IL-6), monocyte chemotactic protein 1 (Mcp1), and hepatic triglycerides. In addition, the mRNA expression levels of Toll-like receptor 2 (Tlr2), Toll-like receptor 4 (Tlr4), tumor necrosis factor alpha (Tnf-α), Mcp1, and peroxisome proliferator-activated receptor gamma (Ppar-γ) significantly increased. Only abundant lipid accumulation and a few inflammatory reactions were observed in group HL-HFD. Relative abundance of Bacteroidetes and Firmicutes shifted in the HFD-fed mice. Furthermore, the relative abundance of Streptococcaceae was the highest in group NASH-HFD. Nevertheless, obesity-related Lactobacillaceae were significantly upregulated in HL-HFD mice. Our results revealed that the gut microbiota from NASH Patients aggravated hepatic steatosis and inflammation. These findings might partially explain the NAFLD progress distinctly was related to different compositions of gut microbiota.

Original languageEnglish
Article number1220
JournalNutrients
Volume9
Issue number11
DOIs
Publication statusPublished - Nov 2017

Keywords

  • Gut microbiota
  • High-fat diet
  • Humanized gnotobiotic mice
  • Nonalcoholic fatty liver disease

ASJC Scopus subject areas

  • Food Science
  • Nutrition and Dietetics

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