Gut bacteria from multiple sclerosis patients modulate human T cells and exacerbate symptoms in mouse models
By Egle Cekanaviciute, Bryan B. Yoo, T. Runia, Justine W. Debelius, Sneha Singh, Charlotte A. Nelson, R. Kanner, Yadira Bencosme, Y. Lee, Stephen L. Hauser and 9 more. Proceedings of the National Academy of Sciences of the United States of America, 2017
901 citations recorded by the source corpus.
Significance We have experimentally investigated the immunoregulatory effects of human gut microbiota in multiple sclerosis (MS). We have identified specific bacteria that are associated with MS and demonstrated that these bacteria regulate T lymphocyte-mediated adaptive immune responses and contribute to the proinflammatory environment in vitro and in vivo. Thus, our results expand the knowledge of the microbial regulation of immunity and may provide a basis for the development of microbiome-based therapeutics in autoimmune diseases. 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.
Subfields: Dermatology, Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/e8606a0d9c11b00e6331725623500670596e2edc
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Citations in the corpus
- Impact of microbiota on central nervous system and neurological diseases: the gut-brain axis (2019, background): “Transplantation of these bacteria from patients with MS into GF mice leads to the exacerbation of EAE via increased proinflammatory T cell response and weakened Treg response [146].”
- The gut microbiome: Relationships with disease and opportunities for therapy (2018, background): “Gut microbiota perturbation has also been described in adult (Cekanaviciute et al., 2017) and pediatric (Tremlett et al.”
- Human gut microbiome: hopes, threats and promises (2018, background): “114 115 Strikingly, the studies by Berer et al and Cekanaviciute et al focused their attention on the increased abundance of A. muciniphila in the faecal material of patients with MS.”