Dietary oils modify the host immune response and colonic tissue damage followingCitrobacter rodentiuminfection in mice

Inflammatory bowel disease is an intestinal inflammatory disorder of multifactorial origin, in which diets that favor high n-6 and low n-3 fatty acids have been implicated. The present study addressed whether dietary n-6 and n-3 fatty acids alter colonic mucosal response to Citrobacter rodentium (C. rodentium) infection. Mice were fed diets identical except for fatty acids, with an energy percentage of 15% 18:2n-6 and <0.06% 18:3n-3, 4.2% 18:2n-6 and 1.9% 18:3n-3, or 1.44% 20:5n-3, 4.9% 22:6n-3, 0.32% 18:2n-6, and 0.12% 18:3n-3 from safflower, canola, or fish oil, respectively for 3 wk before infection. Dietary oils had no effect on colonic C. rodentium growth but altered colon 20:4n-6/(20:5n-3+22:6n-3) with 9.40 ± 0.06, 1.94 ± 0.08, and 0.32 ± 0.03% in colon phosphatidylcholine and 3.82 ± 0.18, 1.14 ± 0.02, and 0.30 ± 0.02% in phosphatidylethanolamine of mice fed safflower, canola, or fish oil, respectively. At 10 days postinfection, histological damage, F4/80-positive macrophages, and myeloperoxidase-positive neutrophils in colonic mucosa were higher in infected mice fed safflower than fish oil. Colon gene transcripts for macrophage inflammatory protein 2, keratinocyte cytokine, and monocyte chemoattractant protein 1 expression were significantly higher in infected mice fed safflower than canola or fish oil; IFN-γ, IL-6, and IL-17A expression were significantly elevated in mice fed safflower rather than fish oil; and IL-10 was significantly higher in mice fed fish oil rather than canola or safflower oil. This study demonstrates that oils high in 18:2n-6 with minimal n-3 fatty acids exacerbate mucosal immune response, whereas oils high in n-3 fatty acids attenuate mucosal immune response to C. rodentium. These studies implicate dietary oils as environmental modifiers of intestinal inflammation in response to infection.