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

Francesca Cignarella, Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Claudia Cantoni, Department of Neurology, Washington University School of Medicine, Campus Box 8111, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.Follow
Laura Ghezzi, 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.
Amber Salter, Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
Yair Dorsett, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Lei Chen, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Daniel Phillips, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
George M. Weinstock, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA.
Luigi Fontana, 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.
Anne H. Cross, 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.
Yanjiao Zhou, Jackson Laboratory for Genomic Medicine, Farmington, CT, USA. Electronic address: yazhou@uchc.edu.
Laura Piccio, 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.

Document Type

Article

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

Medical Subject Headings

Adipokines (blood); Adult; Animals; Autoimmunity; Bacteroidaceae (metabolism); Central Nervous System (immunology); Encephalomyelitis, Autoimmune, Experimental (diet therapy, immunology, microbiology); Fasting; Female; Gastrointestinal Microbiome; Humans; Lactobacillaceae (metabolism); Mice; Mice, Inbred C57BL; Middle Aged; Multiple Sclerosis (diet therapy, immunology, microbiology); Pilot Projects; T-Lymphocytes, Regulatory (immunology); Th17 Cells (immunology)

Publication Date

6-5-2018

Publication Title

Cell metabolism

E-ISSN

1932-7420

Volume

27

Issue

6

First Page

1222

Last Page

1235.e6

PubMed ID

29874567

Digital Object Identifier (DOI)

10.1016/j.cmet.2018.05.006

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