Dietary fatty acids directly impact central nervous system autoimmunity via the small intestine


  • A. Haghikia
  • S. Jörg
  • A. Duscha
  • J. Berg
  • A. Manzel
  • A. Waschbisch
  • A. Hammer
  • D.H. Lee
  • C. May
  • N. Wilck
  • A. Balogh
  • A.I. Ostermann
  • N.H. Schebb
  • D.A. Akkad
  • D.A. Grohme
  • M. Kleinewietfeld
  • S. Kempa
  • J. Thöne
  • S. Demir
  • D.N. Müller
  • R. Gold
  • R.A. Linker


  • Immunity


  • Immunity 43 (4): 817-829


  • Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.