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Cell Metab. 2018 Jun 5;27(6):1222-1235.e6. doi: 10.1016/j.cmet.2018.05.006.

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

Author information

1
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
2
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Neurology Unit, Department of Pathophysiology and Transplantation, University of Milan, Fondazione Cà Granda, IRCCS Ospedale Policlinico, Milan, Italy.
3
Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
4
Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
5
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Clinical and Experimental Sciences, Brescia University Medical School, Brescia, Italy; CEINGE Biotecnologie Avanzate, Napoli, Italy.
6
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA.
7
Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: yazhou@uchc.edu.
8
Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, MO, USA. Electronic address: picciol@wustl.edu.

Abstract

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.

KEYWORDS:

diet; experimental autoimmune encephalomyelitis; gut microbiota; intermittent fasting; multiple sclerosis

PMID:
29874567
DOI:
10.1016/j.cmet.2018.05.006

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