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Published November 2018 | Supplemental Material + Submitted + Published
Journal Article Open

Multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria

Abstract

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system characterized by adaptive and innate immune system dysregulation. Recent work has revealed moderate alteration of gut microbial communities in subjects with MS and in experimental, induced models. However, a mechanistic understanding linking the observed changes in the microbiota and the presence of the disease is still missing. Chloroform-resistant, spore-forming bacteria, which primarily belong to the classes Bacilli and Clostridia in the phylum Firmicutes, have been shown to exhibit immunomodulatory properties in vitro and in vivo, but they have not yet been characterized in the context of human disease. This study addresses the community composition and immune function of this bacterial fraction in MS. We identify MS-associated spore-forming taxa (primarily in the class Clostridia) and show that their presence correlates with impaired differentiation of IL-10-secreting, regulatory T lymphocytes in vitro. Colonization of antibiotic-treated mice with spore-forming bacteria allowed us to identify some bacterial taxa favoring IL-10^+ lymphocyte differentiation and others inducing differentiation of proinflammatory, IFN-γ^+ T lymphocytes. However, when fed into antibiotic-treated mice, both MS and control-derived spore-forming bacteria were able to induce similar IL-10-expressing Treg immunoregulatory responses, thus ameliorating symptoms of experimental allergic encephalomyelitis (EAE). Our analysis also identified Akkermansia muciniphila as a key organism that may interact either directly or indirectly with spore-forming bacteria to exacerbate the inflammatory effects of MS-associated gut microbiota. Thus, changes in the spore-forming fraction may influence T lymphocyte-mediated inflammation in MS. This experimental approach of isolating a subset of microbiota based on its functional characteristics may be useful to investigate other microbial fractions at greater depth.

Additional Information

© 2018 Cekanaviciute et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. Received 8 June 2018 Accepted 5 October 2018 Published 6 November 2018. Data availability: Raw and processed data are available at the UCSF datashare (DASH) platform (https://doi.org/10.7272/Q6FB5136). We thank all subjects who participated in this study. Funding was provided by a grant (CA_1072-A-7) from the National MS Society (S.E.B.). A.-K.P. was supported by postdoctoral fellowships from the Swiss National Science Foundation (P2SKP3_164938/1/P300PB_177927/1). This study was also supported by a generous gift from the Valhalla Charitable Foundation. S.E.B. is the Heidrich Family and Friends Endowed Chair in Neurology.

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Published - e00083-18.full.pdf

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Supplemental Material - inline-supplementary-material-5.pdf

Supplemental Material - inline-supplementary-material-6.pdf

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Created:
August 19, 2023
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