Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 28, 2020; 26(40): 6224-6240
Published online Oct 28, 2020. doi: 10.3748/wjg.v26.i40.6224
New strain of Pediococcus pentosaceus alleviates ethanol-induced liver injury by modulating the gut microbiota and short-chain fatty acid metabolism
Xian-Wan Jiang, Ya-Ting Li, Jian-Zhong Ye, Long-Xian Lv, Li-Ya Yang, Xiao-Yuan Bian, Wen-Rui Wu, Jing-Jing Wu, Ding Shi, Qing Wang, Dai-Qiong Fang, Kai-Cen Wang, Qiang-Qiang Wang, Yan-Meng Lu, Jiao-Jiao Xie, Lan-Juan Li
Xian-Wan Jiang, Ya-Ting Li, Jian-Zhong Ye, Long-Xian Lv, Li-Ya Yang, Xiao-Yuan Bian, Wen-Rui Wu, Jing-Jing Wu, Ding Shi, Qing Wang, Dai-Qiong Fang, Kai-Cen Wang, Qiang-Qiang Wang, Yan-Meng Lu, Jiao-Jiao Xie, Lan-Juan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Author contributions: Jiang XW, Lv LX and Li LJ conceptualized the study; Li YT, Ye JZ and Wang KC performed data curation; Wu JJ and Wang Q completed the formal analysis; Li LJ provided funding acquisition; Wang KC, Yang LY and Lu YM completed the experiments; Jiang XW, Li YT, Ye JZ, Bian XY and Wu WR supplied the methodology; Li LJ administered the project; Ye JZ and Fang DQ provided software support; Lv LX supervised the study; Yang LY and Xie JJ finished the validation; Shi D visualized the data; Jiang XW and Wang QQ wrote the original draft; Jiang XW and Li LJ reviewed and edited the manuscript.
Supported by National Natural Science Foundation of China, No. 81330011, No. 81790631, No. 81570512, and No. 81790633; Science Fund for Creative Research Groups of the National Natural Science Foundation of China, No. 81121002; and National Key Research and Development Program of China, No. 2018YFC2000500.
Institutional review board statement: This study was reviewed and approved by the review board of The First Affiliated Hospital, College of Medicine, Zhejiang University.
Institutional animal care and use committee statement: All experimental procedures were approved by the Animal Care and Use Committee of The First Affiliated Hospital, College of Medicine, Zhejiang University.
Conflict-of-interest statement: The authors have no conflicts of interest related to this study to disclose.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE Guidelines, and the manuscript was prepared and revised according to the ARRIVE Guidelines.
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/
Corresponding author: Lan-Juan Li, PhD, Academic Research, Doctor, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Received: June 23, 2020
Peer-review started: June 23, 2020
First decision: July 28, 2020
Revised: August 8, 2020
Accepted: September 11, 2020
Article in press: September 11, 2020
Published online: October 28, 2020
ARTICLE HIGHLIGHTS
Research background

Gut microbiota dysbiosis plays an important role in the progression of ethanol-induced liver injury, and microbe-based therapy including probiotics, prebiotics and fecal microbiota transplantation, has emerged as a prospective treatment option for patients with alcoholic liver disease (ALD).

Research motivation

Pediococcus pentosaceus (P. pentosaceus) belongs to the Lactobacillaceae family and is widely used as a probiotic. P. pentosaceus CGMCC 7049 is a newly isolated strain of bacteria that has been shown to be resistant to acid and bile salts, with a high tolerance to ethanol. Moreover, further studies are needed to determine the effects of P. pentosaceus supplementation on ethanol-induced liver injury.

Research objectives

The aim of our study was to evaluate the protective effect of the probiotic P. pentosaceus on an experimental ALD model and to investigate the potential mechanisms.

Research methods

P. pentosaceus CGMCC 7049 was isolated from healthy adults in our laboratory. The chronic plus binge NIAAA model was used to evaluate the protective effects. Mice were randomly divided into three groups: the control group received a pair-fed control diet and oral gavage with sterile phosphate buffer saline (PBS), the EtOH group received 5% ethanol Lieber-DeCarli diet and oral gavage with PBS, and the P. pentosaceus group received a 5% ethanol Lieber-DeCarli diet and P. pentosaceus treatment. Gut and liver tissue samples were harvested to assess the gut barrier function and liver injury-related parameters. Fresh cecal contents were collected for the 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analyses.

Research results

The P. pentosaceus treatment improved ethanol-induced liver injury by reducing alanine aminotransferase, aspartate transaminase and triglyceride levels, and neutrophil infiltration, which was accompanied by decreased levels of endotoxin and inflammatory cytokines. In addition, P. pentosaceus administration increased the expression of a tight junction protein, mucin proteins and antibacterial peptides to improve the gut barrier function. Ethanol administration induced intestinal dysbiosis and increased the relative abundance of pathogenic Escherichia and Staphylococcus but depleted SCFA-producing bacteria. In contrast, P. pentosaceus treatment increased the microbial diversity and restored the relative abundance of SCFA-producing bacteria, such as Prevotella, Clostridium and Akkermansia, and increased the production of propionic acid and butyric acid.

Research conclusions

Based on the results of the present study, the newly isolated strain of P. pentosaceus was an effective treatment that protected against ethanol-induced liver injury by modulating the gut microbiota and improving SCFA metabolism and gut barrier function.

Research perspectives

An ethanol-resistant strain of probiotic P. pentosaceus alleviated ethanol-induced liver injury in a chronic plus binge animal model, which might represent a promising microbe-based therapy for patients with ALD.