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

被引:444
作者
Cignarella, Francesca [1 ]
Cantoni, Claudia [1 ]
Ghezzi, Laura [1 ,2 ]
Salter, Amber [3 ]
Dorsett, Yair [4 ]
Chen, Lei [4 ]
Phillips, Daniel [4 ]
Weinstock, George M. [4 ]
Fontana, Luigi [5 ,6 ,7 ]
Cross, Anne H. [1 ,8 ]
Zhou, Yanjiao [4 ,9 ]
Piccio, Laura [1 ,8 ]
机构
[1] Washington Univ, Sch Med, Dept Neurol, Campus Box 8111,660 S Euclid Ave, St Louis, MO 63110 USA
[2] Univ Milan, Fdn Ca Granda, IRCCS Osped Policlin, Neurol Unit,Dept Pathophysiol & Transplantat, Milan, Italy
[3] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA
[4] Jackson Lab Genom Med, Farmington, CT 06032 USA
[5] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA
[6] Brescia Univ, Med Sch, Dept Clin & Expt Sci, Brescia, Italy
[7] CEINGE Biotecnol Avanzate, Naples, Italy
[8] Washington Univ, Sch Med, Hope Ctr Neurol Disorders, St Louis, MO 63110 USA
[9] Univ Connecticut, Hlth Ctr, Dept Med & OB GYN, 263 Farmington Ave, Farmington, CT 06030 USA
关键词
SEGMENTED FILAMENTOUS BACTERIA; SCLEROSIS FUNCTIONAL COMPOSITE; PROTEIN-COUPLED RECEPTOR; CHAIN FATTY-ACIDS; BODY-MASS INDEX; MULTIPLE-SCLEROSIS; T-CELLS; DIET; RISK; OBESITY;
D O I
10.1016/j.cmet.2018.05.006
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1222 / +
页数:20
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