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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-deficient diet-induced nonalcoholic steatohepatitis
Jian-Zhong Ye, Ya-Ting Li, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Li-Ya Yang, Xiao-Yuan Bian, Jing-Jing Wu, Qing Wang, Xian-Wan Jiang, Cong-Gao Peng, Wan-Chun Ye, Peng-Cheng Xia, Lan-Juan Li
Jian-Zhong Ye, Ya-Ting Li, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Li-Ya Yang, Xiao-Yuan Bian, Jing-Jing Wu, Qing Wang, Xian-Wan Jiang, Cong-Gao Peng, Lan-Juan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Jian-Zhong Ye, Ya-Ting Li, Wen-Rui Wu, Ding Shi, Dai-Qiong Fang, Li-Ya Yang, Xiao-Yuan Bian, Jing-Jing Wu, Qing Wang, Xian-Wan Jiang, Cong-Gao Peng, Lan-Juan Li, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Wan-Chun Ye, Department of Chemotherapy 2, Wenzhou Central Hospital, Wenzhou 325000, Zhejiang Province, China
Peng-Cheng Xia, Department of Clinical Laboratory, Tai’an Central Hospital, Tai’an 271000, Shandong Province, China
Author contributions: Ye JZ, Li YT and Wu WR have contributed equally to this work. Ye JZ, Li YT, Wu WR and Li LJ conceived and designed the experiments; Ye JZ, Li YT and Wu WR performed the experiments; Ye JZ, Shi D, Fang DQ, Yang LY and Bian XY analyzed the data; Wu JJ, Wang Q and Jiang XW contributed analysis tools; Ye JZ, Li YT and Wu WR wrote the manuscript; Ye JZ and Peng CG conducted a critical revision of the manuscript for important intellectual content; Ye WC, Xia PC and Li LJ reviewed the manuscript; all authors have approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81330011, No. 81790631, and No. 81790633; the Science Fund for Creative Research Groups of the National Natural Science Foundation of China, No. 81721091; and the National Basic Research Program of China (973 program), No. 2013CB531401.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Institutional Animal Care and Use Committee of Zhejiang University School of Medicine (Permit number: 2017-591).
Conflict-of-interest statement: There is no conflict of interest in this study.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The ARRIVE Guidelines have been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lan-Juan Li, MD, PhD, Academic Research, Doctor, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, No.79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236759 Fax: +86-571-87236459
Received: February 28, 2018
Peer-review started: March 1, 2018
First decision: March 15, 2018
Revised: March 27, 2018
Accepted: May 11, 2018
Article in press: May 11, 2018
Published online: June 21, 2018
ARTICLE HIGHLIGHTS
Research background
The contributing role of the gut microbiota in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been extensively studied.
Research motivation
Gut microbiota dysbiosis in NASH is mainly depicted as an endpoint, and little is known regarding the microbiota disturbances during NASH progression.
Research objectives
Our goal was to investigate dynamic changes in the gut microbiota and its metabolism during the progression from simple hepatic steatosis to NASH in mice fed a methionine-choline-deficient (MCD) diet.
Research methods
C57BL/6J mice were equally divided into four groups and fed either a methionine-choline-sufficient diet for 2 or 4 wk (the Control 2w group and Control 4w group, respectively) or the MCD diet for 2 or 4 wk (the MCD 2w group and MCD 4w group, respectively) (n = 6 per group). Liver injury, fibrosis, intestinal barrier function, and the fecal microbiome and metabolome were studied.
Research results
The mice fed with the MCD diet for 2 wk developed simple hepatic steatosis, which progressed to prominent NASH with liver fibrosis after 4 wk. Compared with the control diet, the MCD diet induced gradual intestinal barrier impairment and gut microbiota dysbiosis; the fecal metabolomic profile was also substantially altered by the MCD diet.
Research conclusions
The MCD diet induced persistent alteration of the gut microbiota and metabolome.
Research perspectives
We may have for the first time shown that an MCD diet induced persistent gut microbiota and metabolome deterioration. Fundamental observations of these alterations will provide new insight into NASH-associated intestinal disorder and gut-targeted therapies for NASH.
