TY - JOUR
T1 - Intermittent Fasting Confers Protection in CNS Autoimmunity by Altering the Gut Microbiota
AU - Cignarella, Francesca
AU - Cantoni, Claudia
AU - Ghezzi, Laura
AU - Salter, Amber
AU - Dorsett, Yair
AU - Chen, Lei
AU - Phillips, Daniel
AU - Weinstock, George M.
AU - Fontana, Luigi
AU - Cross, Anne H.
AU - Zhou, Yanjiao
AU - Piccio, Laura
N1 - Funding Information:
We thank Kathleen Obert for assistance as the nutritionist of the human study; Bob Mikesell, Bryan Bollman, Mike Ramsbottom, and Neville Rapp for technical assistance; Drs. Erin Longbrake, Becky Parks, Robert Naismith, and Gregory Wu for referring patients to the human study; Dr. John Holloszy for advice; all MS patients who participated in this study; the study coordinators Linda Heinrich, Courtney Dula, Samantha Lancia, Susan Fox, and Bridgette Clay; Dr. Giuseppe Matarese for advice on Treg analyses. This project was supported by grant no. R01 NS102633-01 to L.P. and Y.Z. from the NIH /NINDS. This work was supported also by the Office of the Assistant Secretary of Defense for Health Affairs, through the Multiple Sclerosis Research Program under Award No. W81XWH-14-1-0156. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Additional funding for this study was provided by Fondazione Italiana Sclerosi Multipla ( FISM ; 2014/R/15) and the Longer Life Foundation (an RGA/Washington University Partnership) that provided support for the initial part of the human study in MS patients. A.H.C. was supported in part by the Manny & Rosalyn Rosenthal – Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. L.P. was supported by the Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society (NMSS, JF 2144A2/1). C.C. was supported during the course of this study by a FISM fellowship (2012/B/1) and subsequently by an NMSS fellowship (FG 2010-A1/2). Patients were seen for this study in the Neuroclinical Research Unit ( NCRU ) supported by grant C06RR014513 .
Funding Information:
We thank Kathleen Obert for assistance as the nutritionist of the human study; Bob Mikesell, Bryan Bollman, Mike Ramsbottom, and Neville Rapp for technical assistance; Drs. Erin Longbrake, Becky Parks, Robert Naismith, and Gregory Wu for referring patients to the human study; Dr. John Holloszy for advice; all MS patients who participated in this study; the study coordinators Linda Heinrich, Courtney Dula, Samantha Lancia, Susan Fox, and Bridgette Clay; Dr. Giuseppe Matarese for advice on Treg analyses. This project was supported by grant no. R01 NS102633-01 to L.P. and Y.Z. from the NIH/NINDS. This work was supported also by the Office of the Assistant Secretary of Defense for Health Affairs, through the Multiple Sclerosis Research Program under Award No. W81XWH-14-1-0156. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense. Additional funding for this study was provided by Fondazione Italiana Sclerosi Multipla (FISM; 2014/R/15) and the Longer Life Foundation (an RGA/Washington University Partnership) that provided support for the initial part of the human study in MS patients. A.H.C. was supported in part by the Manny & Rosalyn Rosenthal ? Dr. John L. Trotter MS Center Chair in Neuroimmunology of the Barnes-Jewish Hospital Foundation. L.P. was supported by the Harry Weaver Neuroscience Scholar of the National Multiple Sclerosis Society (NMSS, JF 2144A2/1). C.C. was supported during the course of this study by a FISM fellowship (2012/B/1) and subsequently by an NMSS fellowship (FG 2010-A1/2). Patients were seen for this study in the Neuroclinical Research Unit (NCRU) supported by grant C06RR014513.
Publisher Copyright:
© 2018 Elsevier Inc.
PY - 2018/6/5
Y1 - 2018/6/5
N2 - 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.
AB - 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.
KW - diet
KW - experimental autoimmune encephalomyelitis
KW - gut microbiota
KW - intermittent fasting
KW - multiple sclerosis
UR - http://www.scopus.com/inward/record.url?scp=85047319979&partnerID=8YFLogxK
U2 - 10.1016/j.cmet.2018.05.006
DO - 10.1016/j.cmet.2018.05.006
M3 - Article
C2 - 29874567
AN - SCOPUS:85047319979
VL - 27
SP - 1222-1235.e6
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 6
ER -