Published online Oct 7, 2018. doi: 10.3748/wjg.v24.i37.4254
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
To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium (AOM/DSS) induced mice model.
C57BL/6 mice were administered AOM/DSS to develop the ulcerative colitis (UC) carcinogenesis model. Mice were treated with 5-ASA (75 mg/kg/d), VSL#3 (1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage 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 were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16s rDNA sequencing method.
VSL#3 significantly reduced the tumor load in 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. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with 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 as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium.
VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.
Core tip: Microbiota and chronic inflammation play an important role in the process of ulcerative colitis (UC)-associated carcinogenesis. Our study found VSL#3 could effectively prevent UC-associated carcinogenesis in azoxymethane/dextran sulfate sodium induced mice and decrease the level of tumor necrosis factor-α and IL-6 in colon tissue. The intestinal microbiota dysbiosis exists in UC-associated carcinogenesis. Supplementary VSL#3 is beneficial for rebalancing the fecal and mucosal intestinal microbiota. Based on the data presented here, VSL#3 may be a potential therapeutic agent for UC-associated carcinogenesis prevention.