Journal Article

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

Nelson, Charlotte A., Lee, Yun Kyung, Yoo, Bryan B., Debelius, Justine W., Hauser, Stephen L., Crabtree-Hartman, Elizabeth, Zhu, Yunjiao, Sand, Ilana Katz, Kanner, Rachel, Bencosme, Yadira, Knight, Rob, Casaccia, Patrizia, Mazmanian, Sarkis K., Gacias, Mar, Runia, Tessel F., Cree, Bruce A. C., Cekanaviciute, Egle, Baranzini, Sergio E., Singh, Sneha

2017

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Acinetobacter calcoaceticus / Akkermansia muciniphila / Animal models / Animals / Bacteria / Biological Sciences / CD25 antigen / CD4 antigen / Cells, Cultured / Central nervous system / Community structure / Digestive system / Disease Models, Animal / Encephalomyelitis, Autoimmune, Experimental - immunology / Encephalomyelitis, Autoimmune, Experimental - microbiology / Encephalomyelitis, Autoimmune, Experimental - pathology / Experimental allergic encephalomyelitis / Female / Foxp3 protein / Gastrointestinal Microbiome / Gastrointestinal tract / Germfree / Human behavior / Humans / Immunology and Inflammation / Inflammation / Interleukin 10 / Intestinal microflora / Intestine / Leukocytes (mononuclear) / Leukocytes, Mononuclear - immunology / Leukocytes, Mononuclear - microbiology / Leukocytes, Mononuclear - pathology / Lymphocytes / Lymphocytes T / Male / Mice / Microbiota / Microorganisms / Multiple sclerosis / Multiple Sclerosis - immunology / Multiple Sclerosis - microbiology / Multiple Sclerosis - pathology / Parabacteroides distasonis / Pathogenesis / Patients / Peripheral blood mononuclear cells / Rodents / SEE COMMENTARY / T-Lymphocytes - immunology / T-Lymphocytes - microbiology / T-Lymphocytes - pathology / T-Lymphocytes, Regulatory - immunology / Therapeutic targets / Transplants