Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis.
Journal
Nutrients
ISSN
2072-6643
Date Issued
2017-11-06
Author(s)
Chiu, Chien-Chao
Ching, Yung-Hao
Li, Yen-Peng
Liu, Ju-Yun
Huang, Yen-Te
Yang, Sien-Sing
Huang, Wen-Ching
Chuang, Hsiao-Li
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 ), Toll-like receptor 4 , tumor necrosis factor alpha (), , and peroxisome proliferator-activated receptor gamma () significantly increased. Only abundant lipid accumulation and a few inflammatory reactions were observed in group HL-HFD. Relative abundance of and shifted in the HFD-fed mice. Furthermore, the relative abundance of was the highest in group NASH-HFD. Nevertheless, obesity-related 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.
Subjects
gut microbiota
high-fat diet
humanized gnotobiotic mice
nonalcoholic fatty liver disease
Type
journal article