Understanding the effect of a ketogenic diet in colitis

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The ketogenic diet (KD) is an established therapeutic approach in childhood epilepsy and its neuroprotective effects have been explored in previous studies. In a preliminary experiment we could show a profound protective effect of prophylactic dietary treatment with a ketogenic diet as compared to a classic high-carbohydrate standard diet in the dextran sodium sulfate (DSS) mouse model of colitis. The aim of this project is to further establish whether and how a KD can protect from experimentally induced colitis in mice, and can alleviate and treat existing colitis disease in mice. In practice we will test (1) the effect and metabolic safety of different diets and KD compositions in two acute and two chronic mouse colitis models. To assess the feasibility and metabolic safety of long-term KD administration we will also perform a long-term study with the tested diets over the natural life span of the C57Bl6 mice used in the colitis experiments. In order to understand underlying protective and metabolic mechanisms and changes we will assess clinically and histopathologically colitis disease activity and - as previous results suggest an increase in mitochondrial function due to KD - we will elucidate the effect of KD on mitochondrial number, protein expression and function in the colon. (2) Furthermore, in order to assess the importance of ketosis in KD as compared to purely low-carbohydrate high-fat diet (LCHFD) these two dietary approaches will be tested in experimental colitis models in mice. We will also directly assess the effect of ketone bodies (administered as ketone esters) as nutrients for prevention and treatment of experimental colitis in association with either standard diet (SD) or LCHFD. (3) The effect of ketogenic diet interventions will also be tested in mouse strains with differences in mitochondrial biogenesis and/or function.