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Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10719-10724. doi: 10.1073/pnas.1711233114. Epub 2017 Sep 11.

Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice.

Author information

1
Hertie Senior Professor Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany.
2
Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximillians University, 81377 Munich, Germany.
3
Department of Neurology, University of California, San Francisco, CA 94143.
4
BGI-Shenzhen, Shenzhen, 518083, China.
5
Department of Neurology, University Hospital Münster, 48149 Münster, Germany.
6
Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany.
7
Institute for Human Genetics, University of California, San Francisco, CA 94143.
8
Munich Cluster for Systems Neurology, Ludwig-Maximillians University, 81377 Munich, Germany.
9
Hertie Senior Professor Group, Max Planck Institute of Neurobiology, 82152 Martinsried, Germany; guru@biochem.mpg.de hwekerle@neuro.mpg.de.
10
Research Group for Neuroinflammation and Mucosal Immunology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.

Abstract

There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis (MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.

KEYWORDS:

experimental autoimmune encephalomyelitis; germ-free mice; gut microbiome; multiple sclerosis; twin study

Comment in

PMID:
28893994
PMCID:
PMC5635914
DOI:
10.1073/pnas.1711233114
[Indexed for MEDLINE]
Free PMC Article

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