P051 Diets enriched in fat and sugar and sex-dependant response to colitis in a mouse model

Abstract

Abstract Background Inflammatory bowel diseases (IBD) are chronic diseases characterized by inflammation of the mucosa linked to an alteration of the intestinal microbiota and overreaction of the immune system. The prevalence of IBD is increasing in industrialized countries where we find a “Western Diet” rich in refined sugars and saturated fats but low in fiber and essential unsaturated fatty acids1. Thus, nutrition seems to be an important environmental factor involved in the occurrence of IBD, however, underlying biological mechanisms are still poorly understood2. Additionally, most studies on colitis focused on males, yet diets effects are often very different according to sex. The aim of this study was therefore to study the sex-dependent effect of a diet enriched in sugar (sucrose) and a diet rich in fat in a mouse model of colitis. Methods Male and female, 9-weeks old C57BL/6 mice were fed 3 diets for 8 weeks: control diet (C), high-fat diet (HF), and high-fat/high-sucrose diet (HFHS). Then, colitis was induced using 3% Dextran sodium sulfate (DSS) for 5 days and kept 5 more days without DSS. The animals were monitored and weighed daily to establish a disease activity index (DAI). Blood and stools were collected monthly from the start of feeding. At the end of the protocol, a colonoscopy was carried out for each group before sacrifice and intestinal tissues were collected. Results DSS-induced colitis was earlier and more severe in both males and females fed high-caloric diets (both HF and HFHS). However, the HFHS diet accelerated DSS-induced colitis in males compared to the HF diet, while the HF diet led to more severe DSS-induced colitis than the HFHS diet in females. Males and females had similar weight gain following the high-caloric diets. Conclusion This difference in response to DSS after consumption of high-caloric diets between males and females indicates that the inflammatory mechanisms seem to differ depending on sex. Recent work reports the same sex-dependent effect in the Il10-/- mouse model3, suggesting that the sex has an impact on the pathophysiology of colitis and is essential to consider when studying IBD.