Dietary conjugated linoleic acid links reduced intestinal inflammation to amelioration of CNS autoimmunity.
Adult
Animals
Autoimmunity
/ drug effects
Dietary Supplements
Encephalomyelitis, Autoimmune, Experimental
/ immunology
Enteritis
/ immunology
Female
Humans
Linoleic Acids, Conjugated
/ pharmacology
Male
Mice
Mice, Inbred C57BL
Monocytes
/ drug effects
Multiple Sclerosis, Relapsing-Remitting
/ immunology
Pilot Projects
Proof of Concept Study
conjugated linoleic acid
dietary supplementation
gut–CNS axis
intestinal inflammation
multiple sclerosis
Journal
Brain : a journal of neurology
ISSN: 1460-2156
Titre abrégé: Brain
Pays: England
ID NLM: 0372537
Informations de publication
Date de publication:
07 05 2021
07 05 2021
Historique:
received:
07
07
2020
revised:
23
10
2020
accepted:
16
11
2020
pubmed:
27
4
2021
medline:
25
9
2021
entrez:
26
4
2021
Statut:
ppublish
Résumé
A close interaction between gut immune responses and distant organ-specific autoimmunity including the CNS in multiple sclerosis has been established in recent years. This so-called gut-CNS axis can be shaped by dietary factors, either directly or via indirect modulation of the gut microbiome and its metabolites. Here, we report that dietary supplementation with conjugated linoleic acid, a mixture of linoleic acid isomers, ameliorates CNS autoimmunity in a spontaneous mouse model of multiple sclerosis, accompanied by an attenuation of intestinal barrier dysfunction and inflammation as well as an increase in intestinal myeloid-derived suppressor-like cells. Protective effects of dietary supplementation with conjugated linoleic acid were not abrogated upon microbiota eradication, indicating that the microbiome is dispensable for these conjugated linoleic acid-mediated effects. Instead, we observed a range of direct anti-inflammatory effects of conjugated linoleic acid on murine myeloid cells including an enhanced IL10 production and the capacity to suppress T-cell proliferation. Finally, in a human pilot study in patients with multiple sclerosis (n = 15, under first-line disease-modifying treatment), dietary conjugated linoleic acid-supplementation for 6 months significantly enhanced the anti-inflammatory profiles as well as functional signatures of circulating myeloid cells. Together, our results identify conjugated linoleic acid as a potent modulator of the gut-CNS axis by targeting myeloid cells in the intestine, which in turn control encephalitogenic T-cell responses.
Identifiants
pubmed: 33899089
pii: 6252379
doi: 10.1093/brain/awab040
pmc: PMC8105041
doi:
Substances chimiques
Linoleic Acids, Conjugated
0
Types de publication
Clinical Trial
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1152-1166Informations de copyright
© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.
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