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

Abstract

Inflammatory Bowel Disease (IBD) appears to be triggered by environmental factors (e.g. diet, microbiota composition) leading to dysregulated immune responses in genetically susceptible individuals. To date, studies exploring the cross-interaction between diet, immune responses and microbiota in the pathology of IBD are limited. A recent study reported that a diet based on milk derived fat led to the expansion of a specific pathobiont resulting in worsened colitis in IL-10-/- mice. In this study, we examined the temporal relationship between diet, the gut microbiota and immune responses in experimental models of Colitis and Colitis-associated Cancer (CAC). Mice were fed lard-based high fat diet (HFD-45%Kcal) or low fat diet (LFD-10%Kcal), followed by AOM injection and 3x DSS-cycles [(1.5%DSS-5 days & water-14 days), CAC-model] or 3xDSS-cycles (Colitis-model). HFD-feeding protected mice from developing colitis and CAC as demonstrated by reduced tumour incidence and numbers, improved colon length, body weight, and histological scores and reduced plasma and colonic/tumor inflammatory mediators. Mice with Colitis and CAC fed with HFD presented an improved microbial diversity, associated with a reduction in Proteobacteria and an increase in Firmicutes and Verrucomicrobia compared to their LFD-fed counterparts. Collectively and contrary to the previous report using a milk fat based diet, we show that lard-based HFD alters the gut microbial populations protecting against colitis and reducing the risk for CAC. The data highlights a far more complex regulation of lard-based HFD on microbiota composition and host immune responses warranting further investigations on lardcomponents and other diets as triggers IBD and CAC pathology. Coliti-associated cancer; high fat diet; microbiota; colitis.