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...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-10-01
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| Series: | mSystems |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mSystems.00083-18 |
| _version_ | 1819200454816432128 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-23T03:32:30Z |
| format | Article |
| id | doaj.art-6dfdfaf1ad03468387c82fa31efe09f9 |
| institution | Directory Open Access Journal |
| issn | 2379-5077 |
| language | English |
| last_indexed | 2024-12-23T03:32:30Z |
| publishDate | 2018-10-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mSystems |
| spelling | doaj.art-6dfdfaf1ad03468387c82fa31efe09f92022-12-21T18:01:38ZengAmerican Society for MicrobiologymSystems2379-50772018-10-013610.1128/mSystems.00083-18Multiple Sclerosis-Associated Changes in the Composition and Immune Functions of Spore-Forming BacteriaEgle Cekanaviciute0Anne-Katrin Pröbstel1Anna Thomann2Tessel F. Runia3Patrizia Casaccia4Ilana Katz Sand5Elizabeth Crabtree6Sneha Singh7John Morrissey8Patrick Barba9Refujia Gomez10Rob Knight11Sarkis Mazmanian12Jennifer Graves13Bruce A. C. Cree14Scott S. Zamvil15Sergio E. Baranzini16UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAIcahn School of Medicine at Mount Sinai, New York, New York, USAIcahn School of Medicine at Mount Sinai, New York, New York, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUniversity of California San Diego, San Diego, California, USACalifornia Institute of Technology, Pasadena, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAUCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, California, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mSystems.00083-18immune mechanismsmultiple sclerosisspore-forming bacteria |
| spellingShingle | 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 mSystems immune mechanisms multiple sclerosis spore-forming bacteria |
| title | 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_short | 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 |
| topic | immune mechanisms multiple sclerosis spore-forming bacteria |
| url | https://journals.asm.org/doi/10.1128/mSystems.00083-18 |
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