Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism.
autoimmune diseases
immune modulation
microbiome
multiple sclerosis
neuroregeneration
propionic acid
regulatory T cells
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
19 03 2020
19 03 2020
Historique:
received:
09
11
2018
revised:
27
10
2019
accepted:
13
02
2020
pubmed:
12
3
2020
medline:
21
10
2020
entrez:
12
3
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 32160527
pii: S0092-8674(20)30212-9
doi: 10.1016/j.cell.2020.02.035
pii:
doi:
Substances chimiques
Propionates
0
propionic acid
JHU490RVYR
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1067-1080.e16Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests R.G. and A.H. have filed a patent on the supportive immunomodulatory effect of C3-C8 aliphatic fatty acids.