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

Francesca Cignarella, Claudia Cantoni, Laura Ghezzi, Amber Salter, Yair Dorsett, Lei Chen, Daniel Phillips, George M. Weinstock, Luigi Fontana, Anne H. Cross, Yanjiao Zhou, Laura Piccio

Research output: Contribution to journalArticle

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. 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.

Original languageEnglish
Pages (from-to)1222-1235.e6
JournalCell Metabolism
Volume27
Issue number6
DOIs
Publication statusPublished - 2018

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Cignarella, F., Cantoni, C., Ghezzi, L., Salter, A., Dorsett, Y., Chen, L., Phillips, D., Weinstock, G. M., Fontana, L., Cross, A. H., Zhou, Y., & Piccio, L. (2018). Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota. Cell Metabolism, 27(6), 1222-1235.e6. https://doi.org/10.1016/j.cmet.2018.05.006