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 mech...

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Autores principales:	Egle Cekanaviciute, Anne-Katrin Pröbstel, Anna Thomann, Tessel F. Runia, Patrizia Casaccia, Ilana Katz Sand, Elizabeth Crabtree, Sneha Singh, John Morrissey, Patrick Barba, Refujia Gomez, Rob Knight, Sarkis Mazmanian, Jennifer Graves, Bruce A. C. Cree, Scott S. Zamvil, Sergio E. Baranzini
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	immune mechanisms multiple sclerosis spore-forming bacteria Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6dfdfaf1ad03468387c82fa31efe09f9
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spelling	oai:doaj.org-article:6dfdfaf1ad03468387c82fa31efe09f92021-12-02T18:39:45ZMultiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria10.1128/mSystems.00083-182379-5077https://doaj.org/article/6dfdfaf1ad03468387c82fa31efe09f92018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00083-18https://doaj.org/toc/2379-5077ABSTRACT 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. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro. Author Video: An author video summary of this article is available.Egle CekanaviciuteAnne-Katrin PröbstelAnna ThomannTessel F. RuniaPatrizia CasacciaIlana Katz SandElizabeth CrabtreeSneha SinghJohn MorrisseyPatrick BarbaRefujia GomezRob KnightSarkis MazmanianJennifer GravesBruce A. C. CreeScott S. ZamvilSergio E. BaranziniAmerican Society for Microbiologyarticleimmune mechanismsmultiple sclerosisspore-forming bacteriaMicrobiologyQR1-502ENmSystems, Vol 3, Iss 6 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	immune mechanisms multiple sclerosis spore-forming bacteria Microbiology QR1-502
spellingShingle	immune mechanisms multiple sclerosis spore-forming bacteria Microbiology QR1-502 Egle Cekanaviciute Anne-Katrin Pröbstel Anna Thomann Tessel F. Runia Patrizia Casaccia Ilana Katz Sand Elizabeth Crabtree Sneha Singh John Morrissey Patrick Barba Refujia Gomez Rob Knight Sarkis Mazmanian Jennifer Graves Bruce A. C. Cree Scott S. Zamvil Sergio E. Baranzini Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
description	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. IMPORTANCE To address the impact of microbiome on disease development, it is essential to go beyond a descriptive study and evaluate the physiological importance of microbiome changes. Our study integrates computational analysis with in vitro and in vivo exploration of inflammatory properties of spore-forming microbial communities, revealing novel functional correlations. We specifically show that while small differences exist between the microbiomes of MS patients and healthy subjects, these differences are exacerbated in the chloroform-resistant fraction. We further demonstrate that, when purified from MS patients, this fraction is correlated with impaired immunomodulatory responses in vitro. Author Video: An author video summary of this article is available.
format	article
author	Egle Cekanaviciute Anne-Katrin Pröbstel Anna Thomann Tessel F. Runia Patrizia Casaccia Ilana Katz Sand Elizabeth Crabtree Sneha Singh John Morrissey Patrick Barba Refujia Gomez Rob Knight Sarkis Mazmanian Jennifer Graves Bruce A. C. Cree Scott S. Zamvil Sergio E. Baranzini
author_facet	Egle Cekanaviciute Anne-Katrin Pröbstel Anna Thomann Tessel F. Runia Patrizia Casaccia Ilana Katz Sand Elizabeth Crabtree Sneha Singh John Morrissey Patrick Barba Refujia Gomez Rob Knight Sarkis Mazmanian Jennifer Graves Bruce A. C. Cree Scott S. Zamvil Sergio E. Baranzini
author_sort	Egle Cekanaviciute
title	Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
title_short	Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
title_full	Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
title_fullStr	Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
title_full_unstemmed	Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria
title_sort	multiple sclerosis-associated changes in the composition and immune functions of spore-forming bacteria
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/6dfdfaf1ad03468387c82fa31efe09f9
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Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming Bacteria

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