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Human Gut-Derived Commensal Bacteria Suppress CNS Inflammatory and Demyelinating Disease

The human gut is colonized by a large number of microorganisms (∼1013 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide pr...

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Published in:Cell reports (Cambridge) 2017-08, Vol.20 (6), p.1269-1277
Main Authors: Mangalam, Ashutosh, Shahi, Shailesh K., Luckey, David, Karau, Melissa, Marietta, Eric, Luo, Ningling, Choung, Rok Seon, Ju, Josephine, Sompallae, Ramakrishna, Gibson-Corley, Katherine, Patel, Robin, Rodriguez, Moses, David, Chella, Taneja, Veena, Murray, Joseph
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Language:English
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Summary:The human gut is colonized by a large number of microorganisms (∼1013 bacteria) that support various physiologic functions. A perturbation in the healthy gut microbiome might lead to the development of inflammatory diseases, such as multiple sclerosis (MS). Therefore, gut commensals might provide promising therapeutic options for treating MS and other diseases. We report the identification of human gut-derived commensal bacteria, Prevotella histicola, which can suppress experimental autoimmune encephalomyelitis (EAE) in a human leukocyte antigen (HLA) class II transgenic mouse model. P. histicola suppresses disease through the modulation of systemic immune responses. P. histicola challenge led to a decrease in pro-inflammatory Th1 and Th17 cells and an increase in the frequencies of CD4+FoxP3+ regulatory T cells, tolerogenic dendritic cells, and suppressive macrophages. Our study provides evidence that the administration of gut commensals may regulate a systemic immune response and may, therefore, have a possible role in treatment strategies for MS. [Display omitted] •A human gut bacterium has potential as a therapy for multiple sclerosis (MS)•P. histicola can suppress disease in a preclinical animal model of MS•P. histicola suppresses disease by inducing CD4+ FoxP3+ regulatory T cells Mangalam et al. show that P. histicola can suppress autoimmune disease in a preclinical model of multiple sclerosis. Thus, gut bacteria have the potential to be used as a therapy in human diseases.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2017.07.031