P851 Effects of manipulation of the gut microbiota on colon tumorigenesis in AOM-DSS model

The altered intestinal microbial profiles have been known to be associated with colorectal cancer as well as inflammatory bowel diseases. To determine the role of the commensal bacteria in the sequential stages of colitis-associated cancer (CAC), we tried to explore whether the timing of antibiotics-induced gut microbial change affects colon tumorigenesis in the azoxymethane (AOM)-dextran sodium sulphate (DSS)-induced murine CAC model. CAC was induced in the C57BL/6 mice by injection of 12.5 mg/kg AOM followed by three rounds of 2% DSS exposure to elicit colitis. There were a total of six different groups according to the timing of antibiotics administration. After sacrifice of the mice, colonic inflammation, proliferation and tumorigenesis were evaluated. To characterise the change of intestinal microbiota, high throughput Illumina MiSeq sequencing for sequential faeces were performed. Antibiotics treatment with full-time period decreased AOM/DSS-induced tumour numbers per mouse and mean tumour size, histological colitis and dysplasia scores, and pro-inflammatory and proliferatory cytokine expressions compared with AOM/DSS group without antibiotics treatment. Early antibiotics treatment group (from 3 weeks prior to AOM to first round of DSS) showed relatively lower histological scores and the number of tumours developed compared with AOM/DSS group, however, it was not statistically significant. On the contrary, late antibiotics treatment groups (from first or second round of DSS until the end of the study) demonstrated significant lower histological scores and the number of tumours developed compared with AOM/DSS group. Metagenomic sequencing analysis demonstrated that gut microbial community structures were similar between full-time antibiotics treated group and late treatment groups, while other groups showed distinct gut microbial profiles from each other in principal coordinate analysis. There was a positive correlation between the number of tumours and number of operational taxonimic units. The relative abundances of Bacteroidales order and Lachnospiraceae family had a tendency to be positively related to tumour burden. Antibiotics-induced gut microbial change in AOM/DSS murine model, especially at the inflammation period of CAC, could attenuate colon tumorigenesis, suggesting microbial manipulation as a potential therapeutic option in CAC.