PMID- 29113135 OWN - NLM STAT- MEDLINE DCOM- 20180629 LR - 20181113 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 9 IP - 11 DP - 2017 Nov 6 TI - Nonalcoholic Fatty Liver Disease Is Exacerbated in High-Fat Diet-Fed Gnotobiotic Mice by Colonization with the Gut Microbiota from Patients with Nonalcoholic Steatohepatitis. LID - 10.3390/nu9111220 [doi] LID - 1220 AB - 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-alpha), Mcp1, and peroxisome proliferator-activated receptor gamma (Ppar-gamma) 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. FAU - Chiu, Chien-Chao AU - Chiu CC AD - Animal Technology Laboratories, Agricultural Technology Research Institute, Miaoli 350, Taiwan. 1042032@mail.atri.org.tw. FAU - Ching, Yung-Hao AU - Ching YH AD - Department of Molecular Biology and Human Genetics, Tzu Chi University, Hualien 970, Taiwan. yching@mail.tcu.edu.tw. FAU - Li, Yen-Peng AU - Li YP AD - Graduate Institute of Veterinary Pathobiology, National Chung Hsing University, Taichung 402, Taiwan. d106047002@mail.nchu.edu.tw. FAU - Liu, Ju-Yun AU - Liu JY AD - National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan. wide0720@nlac.narl.org.tw. FAU - Huang, Yen-Te AU - Huang YT AD - National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan. evan@nlac.narl.org.tw. FAU - Huang, Yi-Wen AU - Huang YW AUID- ORCID: 0000-0002-5196-7030 AD - Liver Center, Cathay General Hospital Medical Center, Taipei 106, Taiwan. yiwenhuang@ntu.edu.tw. AD - School of Medicine, Taipei Medical University College of Medicine, Taipei 110, Taiwan. yiwenhuang@ntu.edu.tw. FAU - Yang, Sien-Sing AU - Yang SS AD - Liver Center, Cathay General Hospital Medical Center, Taipei 106, Taiwan. jaab@cgh.org.tw. FAU - Huang, Wen-Ching AU - Huang WC AD - Department of Exercise and Health Science, National Taipei University of Nursing and Health Sciences, Taipei 112, Taiwan. wenching@ntunhs.edu.tw. FAU - Chuang, Hsiao-Li AU - Chuang HL AUID- ORCID: 0000-0002-3718-9076 AD - National Laboratory Animal Center, National Applied Research Laboratories, Taipei 115, Taiwan. p650214@nlac.narl.org.tw. LA - eng PT - Journal Article DEP - 20171106 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 SB - IM MH - Adipose Tissue MH - Animals MH - *Diet, High-Fat MH - *Gastrointestinal Microbiome MH - *Germ-Free Life MH - Humans MH - Liver/metabolism/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Non-alcoholic Fatty Liver Disease/*microbiology PMC - PMC5707692 OTO - NOTNLM OT - gut microbiota OT - high-fat diet OT - humanized gnotobiotic mice OT - nonalcoholic fatty liver disease COIS- The authors declare that they have no conflicts of interest. EDAT- 2017/11/09 06:00 MHDA- 2018/06/30 06:00 PMCR- 2017/11/01 CRDT- 2017/11/09 06:00 PHST- 2017/08/25 00:00 [received] PHST- 2017/10/24 00:00 [revised] PHST- 2017/11/02 00:00 [accepted] PHST- 2017/11/09 06:00 [entrez] PHST- 2017/11/09 06:00 [pubmed] PHST- 2018/06/30 06:00 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - nu9111220 [pii] AID - nutrients-09-01220 [pii] AID - 10.3390/nu9111220 [doi] PST - epublish SO - Nutrients. 2017 Nov 6;9(11):1220. doi: 10.3390/nu9111220.