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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
AIM
To investigate changes in gut microbiota and metabolism during nonalcoholic steatohepatitis (NASH) development in mice fed a methionine-choline-deficient (MCD) diet.
METHODS
Twenty-four male C57BL/6J mice were equally divided into four groups and fed a methionine-choline-sufficient diet for 2 wk (Control 2w group, n = 6) or 4 wk (Control 4w group, n = 6) or the MCD diet for 2 wk (MCD 2w group, n = 6) or 4 wk (MCD 4w group, n = 6). Liver injury, fibrosis, and intestinal barrier function were evaluated after 2 and 4 wk of feeding. The fecal microbiome and metabolome were studied using 16s rRNA deep sequencing and gas chromatography-mass spectrometry.
RESULTS
The mice fed the MCD diet presented with simple hepatic steatosis and slight intestinal barrier deterioration after 2 wk. After 4 wk of feeding with the MCD diet, however, the mice developed prominent NASH with liver fibrosis, and the intestinal barrier was more impaired. Compared with the control diet, the MCD diet induced gradual gut microbiota dysbiosis, as evidenced by a marked decrease in the abundance of Alistipes and the (Eubacterium) coprostanoligenes group (P < 0.001 and P < 0.05, respectively) and a significant increase in Ruminococcaceae UCG 014 abundance (P < 0.05) after 2 wk. At 4 wk, the MCD diet significantly reduced the promising probiotic Bifidobacterium levels and markedly promoted Bacteroides abundance (P < 0.05, and P < 0.01, respectively). The fecal metabolomic profile was also substantially altered by the MCD diet: At 2 wk, arachidic acid, hexadecane, palmitic acid, and tetracosane were selected as potential biomarkers that were significantly different in the corresponding control group, and at 4 wk, cholic acid, cholesterol, arachidic acid, tetracosane, and stearic acid were selected.
CONCLUSION
The MCD diet induced persistent alterations in the gut microbiota and metabolome.
Core tip: Nonalcoholic steatohepatitis (NASH) is increasingly prevalent as a remarkable problem worldwide. Increased evidence indicates the critical role of gut microbiota in NASH progression. We aimed to investigate the dynamic alterations in the gut microbiota and the related metabolites during NASH development in mice fed a methionine-choline-deficient (MCD) diet. We for the first time find that the MCD diet may induce persistent gut microbiota and metabolome deterioration.
