Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism
| Autor: | Dominik N. Müller, Sören Gatermann, Johannes Kaisler, Barbara Gisevius, Daniel Zent, Ori Staszewski, Horst Przuntek, Andreas Faissner, Ruth Schneider, Konstanze F. Winklhofer, Carsten Lukas, Tobias Hegelmaier, András Balogh, Sara Del Mare-Roumani, Stefan Kempa, Pascal Träger, Mario M. Zaiss, Aiden Haghikia, Riccardo Troisi, Stefanie Haase, Sivan Amidror, Gereon Poschmann, Alexander Duscha, Nissan Yissachar, Christina David, Gabriele I. Stangl, Kai Stühler, Frank Hirche, Henrik Nielsen, Ralf Gold, Eva Eilers, Megan G. Massa, Verian Bader, Nikolaos Dokalis, Marco Prinz, Sara Gerstein, Sarah Hirschberg, Ralf A. Linker, Jacob Bak Holm, Sofia K. Forslund, Markus Scholz |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Adult
Male Multiple Sclerosis medicine.medical_treatment Disease Pharmacology Biology T-Lymphocytes Regulatory General Biochemistry Genetics and Molecular Biology Immunomodulation 03 medical and health sciences Feces 0302 clinical medicine Atrophy medicine Humans Microbiome Gene 030304 developmental biology Aged 0303 health sciences Multiple sclerosis Neurodegenerative Diseases Immunotherapy Middle Aged medicine.disease Neuroregeneration Disease Progression Th17 Cells Female Propionates 030217 neurology & neurosurgery |
| Zdroj: | Cell. 180(6) |
| ISSN: | 1097-4172 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|