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

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

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.

Trial registration: ClinicalTrials.gov NCT02411838.

Keywords: diet; experimental autoimmune encephalomyelitis; gut microbiota; intermittent fasting; multiple sclerosis.

Publication types

  • Randomized Controlled Trial

MeSH terms

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

Substances

  • Adipokines

Associated data

  • ClinicalTrials.gov/NCT02411838