Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota

• DOI: 10.1016/j.cmet.2018.05.006
• Publication Date: 2018-06-05T14:45:14Z
• Authors: Francesca Cignarella; Claudia Cantoni; Laura Ghezzi; Amber Salter; Yair Dorsett; Lei Chen; Daniel Phillips; George M. Weinstock; Luigi Fontana; Anne H. Cross; Yanjiao Zhou; Laura Piccio
• Keywords: Adult; Central Nervous System; 0301 basic medicine; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Bacteroidaceae; 610; Autoimmunity; Pilot Projects; T-Lymphocytes, Regulatory; Mice; 03 medical and health sciences; Adipokines; Medicine and Health Sciences; Animals; Humans; Life Sciences; Fasting; Middle Aged; Gastrointestinal Microbiome; 3. Good health; Mice, Inbred C57BL; Lactobacillaceae; Th17 Cells; Female; diet; experimental autoimmune encephalomyelitis; gut microbiota; intermittent fasting; multiple sclerosis; Physiology; Molecular Biology; Cell Biology

Multiple sclerosis (MS) is more common in western countries with diet being a potential contributing factor. Here we show that intermittent fasting (IF) ameliorated clinical course and pathology of the MS model, experimental autoimmune encephalomyelitis (EAE). IF led to increased gut bacteria richness, enrichment of the Lactobacillaceae, Bacteroidaceae, and Prevotellaceae families and enhanced antioxidative microbial metabolic pathways. IF altered T cells in the gut with a reduction of IL-17 producing T cells and an increase in regulatory T cells. Fecal microbiome transplantation from mice on IF ameliorated EAE in immunized recipient mice on a normal diet, suggesting that IF effects are at least partially mediated by the gut flora. In a pilot clinical trial in MS patients, intermittent energy restriction altered blood adipokines and the gut flora resembling protective changes observed in mice. In conclusion, IF has potent immunomodulatory effects that are at least partially mediated by the gut microbiome.