Basic Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Oct 7, 2018; 24(37): 4254-4262
Published online Oct 7, 2018. doi: 10.3748/wjg.v24.i37.4254
VSL#3 can prevent ulcerative colitis-associated carcinogenesis in mice
Chun-Sai-Er Wang, Wen-Bin Li, Hong-Ying Wang, Yi-Ming Ma, Xin-Hua Zhao, Hong Yang, Jia-Ming Qian, Jing-Nan Li
Chun-Sai-Er Wang, Wen-Bin Li, Hong Yang, Jia-Ming Qian, Jing-Nan Li, Department of Gastroenterology, PUMC Hospital, CAMS and PUMC, Beijing 100730, China
Hong-Ying Wang, Yi-Ming Ma, Xin-Hua Zhao, National Cancer Center/Cancer Hospital, CAMS and PUMC, Beijing 100021, China
Author contributions: Wang CS and Li WB are the co-first author; Li JN conceived and designed the experiments; Wang CS and Li WB performed the experiments, and analyzed and interpreted the data; Wang CS and Li JN drafted the paper and revised it critically for important intellectual content; Wang HY, Ma YM, Zhao XH, Yang H, and Qian JM offered help during the experiments; all authors approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81370500 and No. 81770559.
Institutional animal care and use committee statement: All animal experiments were conducted in accordance with the recommendations of the Animal Care Ethics and Use Committee of Peking Union Medical College Hospital and approved by the same Committee (XHDW-2015-0032).
Conflict-of-interest statement: To the best of our knowledge, no conflict of interest exists.
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: Jing-Nan Li, MD, Doctor, Department of Gastroenterology, PUMC Hospital, CAMS and PUMC, No.1 Shuai Fu Yuan, Beijing 100730, China. lijn2008@126.com
Telephone: +86-10-69155019 Fax: +86-10-69155017
Received: May 27, 2018
Peer-review started: May 27, 2018
First decision: July 6, 2018
Revised: August 7, 2018
Accepted: August 24, 2018
Article in press: August 24, 2018
Published online: October 7, 2018
Processing time: 127 Days and 19 Hours
ARTICLE HIGHLIGHTS
Research background

Recently, an upward trend has been observed in the incidence of ulcerative colitis (UC) leading to increased clinical attention on UC-associated carcinogenesis.

Research motivation

Existing treatment for UC in the prevention of carcinogenesis involves several risks and side effects with long-term usage. Finding new treatment regimens are essential.

Research objectives

To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in the azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model.

Research methods

C57BL/6 mice were administered AOM/DSS to develop the UC-associated carcinogenesis model. The treatment group was gavaged with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 109 CFU/d), and 5-ASA + VSL#3 from the day of AOM injection for three months (five days/week). The tumor load was compared in each group, and tumor necrosis factor (TNF-α) and interleukin (IL)-6 levels evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing.

Research results

VSL#3 significantly reduced the tumor load in the AOM/DSS-induced mice model, and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group (UC-associated carcinogenesis not induced). Bacillus and Lactococcus were increased after the intervention with 5-ASA and VSL#3, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA + VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Alloprevotella in the model group compared to the control group. Bifidobacterium was increased after supplementation with VSL#3. 5-ASA + VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium.

Research conclusions

In mice, VSL#3 can prevent UC-associated carcinogenesis, reduce the colonic mucosal inflammation levels, and is beneficial for rebalancing the fecal and mucosal intestinal microbiota.

Research perspectives

VSL#3 may be a potential therapeutic agent for UC-associated carcinogenesis prevention based on the data presented here.