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Proc Natl Acad Sci U S A. 2017 Oct 3;114(40):10713-10718. doi: 10.1073/pnas.1711235114. Epub 2017 Sep 11.

Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models.

Author information

1
Department of Neurology, University of California, San Francisco, CA 94158.
2
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA 91125.
3
Center for Microbiome Innovation, University of California, San Diego, La Jolla, CA 92093.
4
Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY 10029.
5
Advanced Science Research Center, City University of New York, New York, NY 10031.
6
Department of Neurology, University of California, San Francisco, CA 94158; sergio.baranzini@ucsf.edu.

Abstract

The gut microbiota regulates T cell functions throughout the body. We hypothesized that intestinal bacteria impact the pathogenesis of multiple sclerosis (MS), an autoimmune disorder of the CNS and thus analyzed the microbiomes of 71 MS patients not undergoing treatment and 71 healthy controls. Although no major shifts in microbial community structure were found, we identified specific bacterial taxa that were significantly associated with MS. Akkermansia muciniphila and Acinetobacter calcoaceticus, both increased in MS patients, induced proinflammatory responses in human peripheral blood mononuclear cells and in monocolonized mice. In contrast, Parabacteroides distasonis, which was reduced in MS patients, stimulated antiinflammatory IL-10-expressing human CD4+CD25+ T cells and IL-10+FoxP3+ Tregs in mice. Finally, microbiota transplants from MS patients into germ-free mice resulted in more severe symptoms of experimental autoimmune encephalomyelitis and reduced proportions of IL-10+ Tregs compared with mice "humanized" with microbiota from healthy controls. This study identifies specific human gut bacteria that regulate adaptive autoimmune responses, suggesting therapeutic targeting of the microbiota as a treatment for MS.

KEYWORDS:

autoimmunity; microbiome; multiple sclerosis

Comment in

PMID:
28893978
PMCID:
PMC5635915
DOI:
10.1073/pnas.1711235114
[Indexed for MEDLINE]
Free PMC Article

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