Intermittent Administration of a Modified Fasting-Mimicking Diet Reduces Intestinal Inflammation and Promotes Repair to Ameliorate Inflammatory Bowel Disease in Mice

Abstract

Recent studies have revealed that calorie restriction is able to modulate immune system and aid in intervention of immune disorders. Inflammatory bowel disease (IBD) is an immune disease in the intestine caused by interplay between genetic susceptibility and environmental factors such as diets. Here we analyzed the therapeutic effect of intermittent calorie restriction with a modified fasting-mimicking diet (FMD) on dextran sodium sulfate (DSS)-induced chronic IBD model in mice. Two cycles of FMD was administered after IBD symptoms occurred in the mice. FMD administration significantly reduced the score of disease activity index (DAI). FMD reversed DSS-mediated shortening of colon length, infiltration of lymphocytes in the crypt of colon, and accumulation of CD4+ cells in the colon and small intestine. The expression of an inflammation marker NLRP3 was also reduced by FMD administration. The percentage of CD4+ T cells in both peripheral blood and spleen was also reduced by FMD. In addition, FMD application reversed DSS-mediated reduction in intestinal stem cell marker Lgr5, while the cell proliferation markers Ki67 and PCNA were increased by FMD. Taken together, these results indicate that in the mouse model of IBD, application of a modified FMD can effectively ameliorate the symptoms and pathogenesis of IBD through reducing the inflammation of intestine and promoting the regeneration and repair of the damaged intestinal epithelium. Funding Statement: This study was supported by research grants from the National Natural Science Foundation of China (31630036 to Y.C.), the Ministry of Science and Technology of China (2016YFA0500103 to Y.C.), and the Chinese Academy of Sciences (XDA12010102, QYZDJ-SSW-SMC008, ZDRW-ZS-2016-8, and CAS Interdisciplinary Innovation Team to Y.C.). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: All animal experimental procedures were reviewed and authorized under the Institutional Animal Care and Use Committee (IACUC) guidelines of Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences with an approval number 2010-AN-8.