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Nutritional Immunology

Partial Replacement of Dietary (n-6) Fatty Acids with Medium-Chain Triglycerides Decreases the Incidence of Spontaneous Colitis in Interleukin-10–Deficient Mice^1,2

³ Health Sciences Research Institute, ⁴ Department of Pathology, and ⁵ Department of Gastroenterology, University Hospital "Germans Trias i Pujol," 08916 Badalona, Spain; ⁶ Network for Biomedical Research in Gastrointestinal and Liver Disease, 08036 Barcelona, Spain; and ⁷ Clinic for Gastroenterology and Hepatology, Department of Internal Medicine, University Hospital, 8091 Zurich, Switzerland

Enteral nutrition has a primary therapeutic effect in active Crohn's disease. It is unknown which nutrient(s) account for this action, but a role for both the amount and type of dietary fat has been postulated. Some clinical and experimental data suggest that medium-chain triglycerides (MCT) may reduce intestinal inflammation. We aimed to assess the effect of replacing part of the dietary fat with MCT on the incidence and severity of colitis in interleukin (IL)-10(–/–) mice under specific pathogen-free conditions. Twenty-four IL-10(–/–) 4-wk-old mice were randomized to receive a control diet based on sunflower oil [(n-6) fatty acids (FA)] and an experimental isocaloric, isonitrogenous diet with 50% sunflower and 50% coconut oil (MCT diet). When the mice were 12 wk old, they were killed and the colon was examined for the presence of colitis, lymphocyte subpopulations and apoptosis, ex vivo cytokine production in supernatant of colon explants, toll-like receptor (TLR)-2 and TLR-9 mRNA, and FA profile in colonic tissue homogenates. Colitis incidence was lower in the IL-10(–/–) mice fed the MCT diet (1/12) than in the mice fed the control diet (8/12; P = 0.03). The histological damage score was also lower in the former (P < 0.0005). Feeding the MCT diet resulted in fewer total and apoptotic intraepithelial CD3+ and lamina propria CD3+CD4+ lymphocytes, as well as downregulated production of IL-6 and interferon-, and reduced TLR-9 mRNA. We conclude that partial replacement of dietary (n-6) FA with MCT decreases the incidence of colitis in a model of spontaneous intestinal inflammation and provide experimental arguments for a possible primary therapeutic effect of MCT in human Crohn's disease.

^* To whom correspondence should be addressed. E-mail: ecabre.germanstrias{at}gencat.cat.

Manuscript received 21 October 2008. Initial review completed 13 November 2008. Revision accepted 16 December 2008.

Published online 6 January 2009.