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Microbiota Analysis Using Two-step PCR and Next-generation 16S rRNA Gene Sequencing
Published on: October 15, 2019
Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models
Egle Cekanaviciute1, Bryan B Yoo2, Tessel F Runia1
1Department of Neurology, University of California, San Francisco, CA 94158.
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.
Insights
Specific gut bacteria influence multiple sclerosis (MS) development. Certain bacteria promote inflammation, while others reduce it, suggesting gut microbiota as a potential therapeutic target for MS.
Area of Science:
- Immunology
- Microbiology
- Neuroscience
Background:
- The gut microbiota plays a crucial role in regulating T cell functions.
- Multiple sclerosis (MS) is a central nervous system (CNS) autoimmune disorder.
- The impact of gut bacteria on MS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the association between gut microbiota composition and MS.
- To identify specific bacterial taxa influencing MS pathogenesis.
- To explore the therapeutic potential of targeting the gut microbiota for MS treatment.
Main Methods:
- Analyzed gut microbiomes of 71 MS patients and 71 healthy controls.
- Assessed the impact of specific bacteria on immune responses in vitro and in vivo.
- Utilized microbiota transplantation from MS patients and healthy controls into germ-free mice.
Main Results:
- Specific bacterial taxa, Akkermansia muciniphila and Acinetobacter calcoaceticus, were increased in MS patients and induced proinflammatory responses.
- Parabacteroides distasonis was reduced in MS patients and stimulated anti-inflammatory T cells.
- Microbiota transplants from MS patients worsened experimental autoimmune encephalomyelitis (EAE) symptoms in mice.
Conclusions:
- Gut bacteria composition is linked to MS pathogenesis.
- Specific bacteria can modulate adaptive autoimmune responses relevant to MS.
- Targeting the gut microbiota represents a promising therapeutic strategy for MS.

