273 High Fat Feeding Alters Gut Microbiota and Protects Mice From Colitis and Colitis-Associated Colorectal Cancer

Background: Environmental factors, such as diet and gut microbial composition, together with immune dysregulation are thought to trigger inflammatory bowel diseases (IBD) in genetically susceptible individuals. Long term chronic inflammation in IBD patients increases the risk of developing colitis-associated colorectal cancer (CAC). To date, studies exploring the cross-interaction among diet, immunity and microbiota are limited. One recent study reported that feeding of a diet based on milk derived fat to IL-10 deficient mice resulted in worsening colitis and promoted the expansion of a specific pathobiont. Aim(s): Here, we have examined the temporal relationship between diet, the gut microbiota and systemic and intestinal immune responses in an experimental model of colitis and colitis-associated cancer. Method(s): Male C57BL/6 mice (n=8-12 per group) were fed lard-based high fat (HF-45% Kcal) diet or low fat (LF-10% Kcal) diet, followed by injection with the carcinogen azoxymethane (AOM) accompanied by 3xDSS cycles [(1.5%DSS-5days & water-14days) - CAC-model] or 3xDSS cycles alone (Colitis model). Plasma and colonic tissue was collected at the end of the study and assayed for plasma cytokines, colonic and tumour cytokine mRNA expression and protein and histology evaluation. Faecal samples were collected at 3 different time points, DNA extracted and compositional analysis of the microbiota was performed by 16S rDNA amplicon pyrosequencing. Result(s): High fat feeding protected mice from developing colitis and CAC on the basis of significantly increasing body weight (p