Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism

Alexander Duscha, Barbara Gisevius, Sarah Hirschberg, Nissan Yissachar, Gabriele I. Stangl, Eva Dawin, Verian Bader, Stefanie Haase, Johannes Kaisler, Christina David, Ruth Schneider, Riccardo Troisi, Daniel Zent, Tobias Hegelmaier, Nikolaos Dokalis, Sara Gerstein, Sara Del Mare-Roumani, Sivan Amidror, Ori Staszewski, Gereon PoschmannKai Stühler, Frank Hirche, Andras Balogh, Stefan Kempa, Pascal Träger, Mario M. Zaiss, Jacob Bak Holm, Megan G. Massa, Henrik Bjørn Nielsen, Andreas Faissner, Carsten Lukas, Sören G. Gatermann, Markus Scholz, Horst Przuntek, Marco Prinz, Sofia K. Forslund, Konstanze F. Winklhofer, Dominik N. Müller, Ralf A. Linker, Ralf Gold, Aiden Haghikia

Research output: Contribution to journalArticlepeer-review

342 Scopus citations

Abstract

Short-chain fatty acids are processed from indigestible dietary fibers by gut bacteria and have immunomodulatory properties. Here, we investigate propionic acid (PA) in multiple sclerosis (MS), an autoimmune and neurodegenerative disease. Serum and feces of subjects with MS exhibited significantly reduced PA amounts compared with controls, particularly after the first relapse. In a proof-of-concept study, we supplemented PA to therapy-naive MS patients and as an add-on to MS immunotherapy. After 2 weeks of PA intake, we observed a significant and sustained increase of functionally competent regulatory T (Treg) cells, whereas Th1 and Th17 cells decreased significantly. Post-hoc analyses revealed a reduced annual relapse rate, disability stabilization, and reduced brain atrophy after 3 years of PA intake. Functional microbiome analysis revealed increased expression of Treg-cell-inducing genes in the intestine after PA intake. Furthermore, PA normalized Treg cell mitochondrial function and morphology in MS. Our findings suggest that PA can serve as a potent immunomodulatory supplement to MS drugs.

Original languageEnglish
Pages (from-to)1067-1080.e16
JournalCell
Volume180
Issue number6
DOIs
StatePublished - 19 Mar 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • autoimmune diseases
  • immune modulation
  • microbiome
  • multiple sclerosis
  • neuroregeneration
  • propionic acid
  • regulatory T cells

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