Basic Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 14, 2017; 23(38): 6983-6994
Published online Oct 14, 2017. doi: 10.3748/wjg.v23.i38.6983
Fecal microbiota transplantation prevents hepatic encephalopathy in rats with carbon tetrachloride-induced acute hepatic dysfunction
Wei-Wei Wang, Yu Zhang, Xiao-Bing Huang, Nan You, Lu Zheng, Jing Li
Wei-Wei Wang, Yu Zhang, Xiao-Bing Huang, Nan You, Lu Zheng, Jing Li, Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Third Military Medical University, Chongqing 400037, China
Author contributions: Wang WW performed the research, analyzed the data, wrote and revised the paper; Zhang Y, Li J and You N performed the research; Zheng L participated in research design; Li J designed the research and participated in the revision of the paper; all authors have read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Third Military Medical University.
Institutional animal care and use committee statement: All experiments on animals were performed in accordance with the “Guide for the Care and Use of Laboratory Animals” (National Institutes of Health, 8th edition, 2011). All procedures involving animals were reviewed and approved by the Animal Care and Research Committee of the Second Affiliated Hospital of Third Military Medical University.
Conflict-of-interest statement: The authors declare no potential conflict of interest for this paper.
Data sharing statement: No additional data are available.
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: Jing Li, PhD, Department of Hepatobiliary Surgery, the Second Affiliated Hospital of Third Military Medical University, 183# Xinqiao zhengjie, Shapingba District, Chongqing 400037, China. xqyylijing@163.com
Telephone: +86-23-68774606 Fax: +86-23-68755606
Received: July 3, 2017
Peer-review started: July 3, 2017
First decision: July 27, 2017
Revised: August 17, 2017
Accepted: September 6, 2017
Article in press: September 5, 2017
Published online: October 14, 2017
Processing time: 108 Days and 2.4 Hours
Abstract
AIM

To investigate whether fecal microbiota transplantation (FMT) prevents hepatic encephalopathy (HE) in rats with carbon tetrachloride (CCl4)-induced acute hepatic dysfunction.

METHODS

A rat model of HE was established with CCl4. Rat behaviors and spatial learning capability were observed, and hepatic necrosis, intestinal mucosal barrier, serum ammonia levels and intestinal permeability were determined in HE rats receiving FMT treatment. Furthermore, the expression of tight junction proteins (Claudin-1, Claudin-6 and Occludin), Toll-like receptor (TLR) 4/TLR9, interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α was examined.

RESULTS

FMT improved rat behaviors, HE grade and spatial learning capability. Moreover, FMT prevented hepatic necrosis and intestinal mucosal barrier damage, leading to hepatic clearance of serum ammonia levels and reduced intestinal permeability. The expression of TLR4 and TLR9, two potent mediators of inflammatory response, was significantly downregulated in the liver of rats treated with FMT. Consistently, circulating pro-inflammatory factors such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were remarkably decreased, indicating that FMT is able to limit systemic inflammation by decreasing the expression of TLR4 and TLR9. Importantly, HE-induced loss of tight junction proteins (Claudin-1, Claudin-6 and Occludin) was restored in intestinal tissues of rats receiving FMT treatment.

CONCLUSION

FMT enables protective effects in HE rats, and it improves the cognitive function and reduces the liver function indexes. FMT may cure HE by altering the intestinal permeability and improving the TLR response of the liver.

Keywords: Fecal microbiota transplantation; Hepatic encephalopathy; Cognitive function; Intestinal permeability; Toll-like receptor

Core tip: In this article, we first established a rat model of hepatic encephalopathy, and then carried on the fecal microbiota transplantation (FMT). Our results suggest that FMT can serve as a kind of new method for the treatment of hepatic encephalopathy, probably better than VSL#3.