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Genetically modified mice have been successfully used as models for inflammatory bowel diseases; however, dietary effects were poorly examined. Here, we studied the effects of particular nutrients and supplements on gut functions related to the knockout of the epithelial caspase-8 gene. Casp8 knockout and control littermates were fed for 4 weeks a control diet (CD) enriched with 10% inulin (CD-Inu) or 5% butyrate (CD-But) while having free access to plain water or water supplemented with 30% fructose (+F). Body weight changes, intestinal inflammation, selected marker for barrier function, and markers of liver steatosis were assessed. Casp8 knockout mice developed ileocolitis accompanied by changes in intestinal barrier morphology and the expression of barrier-related genes such as mucin-2 ( and defensins in the ileum and in the colon. Casp8 knockout mice fed a control diet also showed impaired body weight gain compared to control mice, which was even more pronounced in mice receiving water supplemented with fructose. Furthermore, we observed pronounced liver steatosis and inflammation in some but not all Casp8 knockout mice under a control diet, which was in average similar to that observed in control mice under a fructose-rich diet. Hepatic lipid accumulation, as well as some markers of ileal barrier function, but not intestinal pathohistology or body weight loss, was attenuated by diets enriched with inulin or butyrate, especially in the absence of fructose supplementation. Our data show that ileocolitis, barrier dysfunction and malassimilation in Caspase-8 knockout mice can be partially attenuated by oral inulin or butyrate supplementation.
This article was published in the following journal.
Name: American journal of physiology. Gastrointestinal and liver physiology
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