Supplementing a Specific Synbiotic Can Suppress the Incidence of AOM/DSS-Induced Colorectal Cancer in Mice

Background: Colorectal cancer is a major health concern worldwide. Synbiotic may have a better protective effect on the risk of colorectal cancer than prebiotics / probiotics given alone. More research is needed to develop effective synbiotics.Object: Synbiotics are prepared based on the excellent anti-colitis and colorectal cancer strains screened in the previous study, and it is planned to investigate its effect on colitis associated cancer (CAC) and its mechanism,Methods: 30 of 6-week-old male C57BL/6J mice were randomly divided into blank control group, Azoxymethane/Dextran sodium sulfate (AOM/DSS) model group, and synbiotic intervention group. The colon length, tumor number and size of the mouse were monitored.The inflammation and intestinal barrier function were determined. 16S rRNA sequencing was used to explore gut microbiota structure, and nontargeted metabolomics analysis was performed to investigate metabolite concentrations in fecal samples.and intestinal mucosal transcriptome sequencing were used to observe the changes of gene expression profile in colon tissue.Results: The synbiotic significantly inhibited the tumorigenesis of CAC mice; ameliorated DSS-induced inflammation (especially reduced the expression of IL-23, P<0.05); recovered intestinal barrier integrity (promoted the expression of tight junction protein ZO-1 and Occludin, P<0.001); reversed the changes of microbial composition in the colon of CAC mice. These changes by synbiotic were associated with an increase in the production of SCFAs and a promotion of tryptophan and bile acid metabolism. Especially importantly, the synbiotic inhibited the activation of Wnt/β-catenin pathway during the formation of CAC.Conclusion: Our study demonstrated that the synbiotic can chang the gut microbiota and the gut metabolome in CAC mice； effectively alleviate colon inflammation and intestinal mucosal barrier damage and inhibit the activation of the Wnt/β-catenin signaling pathway to hindering the formation of CAC.Funding Information: We thank the support of grants from National Natural Science Foundation of China (No.31072141), Scientific Research Fund of Hunan Provincial Education Department (No.2019A293), and Hunan Provincial Key Research and Development Program (No. 2019SK2042).Declaration of Interests: The authors declare no competing financial interest.Ethics Approval Statement: The manipulation of animals was approved by Ethics Committee Board of Hunan Normal University, and performed according to the guidelines in accordance with National Institutes of Health guide for the care and use of Laboratory animals (NIH Publications no. 8023, revised 1978).