2. Academic Validation
  3. Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons

Propionic acid promotes neurite recovery in damaged multiple sclerosis neurons

  • Brain Commun. 2024 Jun 3;6(3):fcae182. doi: 10.1093/braincomms/fcae182.
Barbara Gisevius 1,  Alexander Duscha 1 2,  Gereon Poschmann 3 4,  Kai Stühler 3 4,  Jeremias Motte 1,  Anna Lena Fisse 1,  Sanja Augustyniak 1,  Adriana Rehm 1,  Pia Renk 1,  Celina Böse 1,  Diana Hubert 1,  Kathrin Peters 1,  Michelle Jagst 5 6,  André Gömer 5,  Daniel Todt 5 7,  Verian Bader 8,  Marianne Tokic 9,  Sarah Hirschberg 1,  Christos Krogias 1,  Nadine Trampe 1,  Charlotta Coutourier 1,  Carmen Winnesberg 1,  Eike Steinmann 5,  Konstanze Winklhofer 8 10,  Ralf Gold 1,  Aiden Haghikia 1 2
Affiliations

Affiliations

  • 1 Department of Neurology, St. Josef Hospital, Ruhr-University Bochum, 44791 Bochum, Germany.
  • 2 Department of Neurology, Otto-von-Guericke University, 39120 Magdeburg, Germany.
  • 3 Institute of Molecular Medicine, Proteome Research, Medical Faculty and University Hospital, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
  • 4 Molecular Proteomics Laboratory, BMFZ, Heinrich Heine University Düsseldorf, 40335 Düsseldorf, Germany.
  • 5 Department for Molecular and Medical Virology, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 6 Institute of Virology, University of Veterinary Medicine Hannover, 30559 Hannover, Germany.
  • 7 European Virus Bioinformatics Center (EVBC), 07743 Jena, Germany.
  • 8 Department of Molecular Cell Biology, Institute of Biochemistry and Pathobiochemistry, Ruhr-University Bochum, 44801 Bochum, Germany.
  • 9 Department of Medical Informatics, Biometry and Epidemiology, Ruhr University Bochum, 44780 Bochum, Germany.
  • 10 Cluster of Excellence RESOLV, 44801 Bochum, Germany.
PMID: 38894951 DOI: 10.1093/braincomms/fcae182
Abstract

Neurodegeneration in the autoimmune disease multiple sclerosis still poses a major therapeutic challenge. Effective drugs that target the inflammation can only partially reduce accumulation of neurological deficits and conversion to progressive disease forms. Diet and the associated gut microbiome are currently being discussed as crucial environmental risk factors that determine disease onset and subsequent progression. In people with multiple sclerosis, supplementation of the short-chain fatty acid propionic acid, as a microbial metabolite derived from the fermentation of a high-fiber diet, has previously been shown to regulate inflammation accompanied by neuroprotective properties. We set out to determine whether the neuroprotective impact of propionic acid is a direct mode of action of short-chain fatty acids on CNS neurons. We analysed neurite recovery in the presence of the short-chain fatty acid propionic acid and butyric acid in a reverse-translational disease-in-a-dish model of human-induced primary neurons differentiated from people with multiple sclerosis-derived induced pluripotent stem cells. We found that recovery of damaged neurites is induced by propionic acid and butyric acid. We could also show that administration of butyric acid is able to enhance propionic acid-associated neurite recovery. Whole-cell proteome analysis of induced primary neurons following recovery in the presence of propionic acid revealed abundant changes of protein groups that are associated with the chromatin assembly, translational, and metabolic processes. We further present evidence that these alterations in the chromatin assembly were associated with inhibition of histone deacetylase class I/II following both propionic acid and butyric acid treatment, mediated by Free Fatty Acid Receptor signalling. While neurite recovery in the presence of propionic acid is promoted by activation of the anti-oxidative response, administration of butyric acid increases neuronal ATP synthesis in people with multiple sclerosis-specific induced primary neurons.

Keywords

gut microbiome metabolites; microbiome–gut–brain axis; neurite recovery; neurodegeneration.

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