TY - JOUR
T1 - Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota
AU - Cignarella, Francesca
AU - Cantoni, Claudia
AU - Ghezzi, Laura
AU - Salter, Amber
AU - Dorsett, Yair
AU - Chen, Lei
AU - Phillips, Daniel
AU - Weinstock, George M.
AU - Fontana, Luigi
AU - Cross, Anne H.
AU - Zhou, Yanjiao
AU - Piccio, Laura
N1 - Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/6/5
Y1 - 2018/6/5
N2 - 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. Intermittent fasting confers protection in the multiple sclerosis animal model through effects on the gut microbiota; similar changes to the gut microbiota were observed in relapsing multiple sclerosis patients undergoing intermittent energy restriction.
AB - 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. Intermittent fasting confers protection in the multiple sclerosis animal model through effects on the gut microbiota; similar changes to the gut microbiota were observed in relapsing multiple sclerosis patients undergoing intermittent energy restriction.
KW - diet
KW - experimental autoimmune encephalomyelitis
KW - gut microbiota
KW - intermittent fasting
KW - multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85047319979&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2018.05.006
DO - 10.1016/j.cmet.2018.05.006
M3 - Article
C2 - 29874567
AN - SCOPUS:85047319979
SN - 1550-4131
VL - 27
SP - 1222-1235.e6
JO - Cell metabolism
JF - Cell metabolism
IS - 6
ER -