The gut microbiota in multiple sclerosis varies with disease activity
Abstract Background Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact throu...
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| Format: | Article |
| Language: | English |
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BMC
2023-01-01
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| Series: | Genome Medicine |
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| Online Access: | https://doi.org/10.1186/s13073-022-01148-1 |
| _version_ | 1797958576362225664 |
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| author | Florence Thirion Finn Sellebjerg Yong Fan Liwei Lyu Tue H. Hansen Nicolas Pons Florence Levenez Benoit Quinquis Evelina Stankevic Helle B. Søndergaard Thomas M. Dantoft Casper S. Poulsen Sofia K. Forslund Henrik Vestergaard Torben Hansen Susanne Brix Annette Oturai Per Soelberg Sørensen Stanislav D. Ehrlich Oluf Pedersen |
| author_facet | Florence Thirion Finn Sellebjerg Yong Fan Liwei Lyu Tue H. Hansen Nicolas Pons Florence Levenez Benoit Quinquis Evelina Stankevic Helle B. Søndergaard Thomas M. Dantoft Casper S. Poulsen Sofia K. Forslund Henrik Vestergaard Torben Hansen Susanne Brix Annette Oturai Per Soelberg Sørensen Stanislav D. Ehrlich Oluf Pedersen |
| author_sort | Florence Thirion |
| collection | DOAJ |
| description | Abstract Background Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. Methods Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. Results We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-β, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. Conclusions Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials. |
| first_indexed | 2024-04-11T00:20:54Z |
| format | Article |
| id | doaj.art-92667d91f9624abab5f3c3539b861d21 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-11T00:20:54Z |
| publishDate | 2023-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-92667d91f9624abab5f3c3539b861d212023-01-08T12:17:30ZengBMCGenome Medicine1756-994X2023-01-0115111710.1186/s13073-022-01148-1The gut microbiota in multiple sclerosis varies with disease activityFlorence Thirion0Finn Sellebjerg1Yong Fan2Liwei Lyu3Tue H. Hansen4Nicolas Pons5Florence Levenez6Benoit Quinquis7Evelina Stankevic8Helle B. Søndergaard9Thomas M. Dantoft10Casper S. Poulsen11Sofia K. Forslund12Henrik Vestergaard13Torben Hansen14Susanne Brix15Annette Oturai16Per Soelberg Sørensen17Stanislav D. Ehrlich18Oluf Pedersen19Université Paris-Saclay, INRAE, MGPDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – RigshospitaletNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenUniversité Paris-Saclay, INRAE, MGPUniversité Paris-Saclay, INRAE, MGPUniversité Paris-Saclay, INRAE, MGPNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – RigshospitaletCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg University HospitalNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenExperimental and Clinical Research Center, A Cooperation of Charité–Universitätsmedizin and the Max-Delbrück CenterNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenDepartment of Biotechnology and Biomedicine, Technical University of DenmarkDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – RigshospitaletDanish Multiple Sclerosis Center, Department of Neurology, Copenhagen University Hospital – RigshospitaletUniversité Paris-Saclay, INRAE, MGPNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Science, University of CopenhagenAbstract Background Multiple sclerosis is a chronic immune-mediated disease of the brain and spinal cord resulting in physical and cognitive impairment in young adults. It is hypothesized that a disrupted bacterial and viral gut microbiota is a part of the pathogenesis mediating disease impact through an altered gut microbiota-brain axis. The aim of this study is to explore the characteristics of gut microbiota in multiple sclerosis and to associate it with disease variables, as the etiology of the disease remains only partially known. Methods Here, in a case-control setting involving 148 Danish cases with multiple sclerosis and 148 matched healthy control subjects, we performed shotgun sequencing of fecal microbial DNA and associated bacterial and viral microbiota findings with plasma cytokines, blood cell gene expression profiles, and disease activity. Results We found 61 bacterial species that were differentially abundant when comparing all multiple sclerosis cases with healthy controls, among which 31 species were enriched in cases. A cluster of inflammation markers composed of blood leukocytes, CRP, and blood cell gene expression of IL17A and IL6 was positively associated with a cluster of multiple sclerosis-related species. Bacterial species that were more abundant in cases with disease-active treatment-naïve multiple sclerosis were positively linked to a group of plasma cytokines including IL-22, IL-17A, IFN-β, IL-33, and TNF-α. The bacterial species richness of treatment-naïve multiple sclerosis cases was associated with number of relapses over a follow-up period of 2 years. However, in non-disease-active cases, we identified two bacterial species, Faecalibacterium prausnitzii and Gordonibacter urolithinfaciens, whose absolute abundance was enriched. These bacteria are known to produce anti-inflammatory metabolites including butyrate and urolithin. In addition, cases with multiple sclerosis had a higher viral species diversity and a higher abundance of Caudovirales bacteriophages. Conclusions Considerable aberrations are present in the gut microbiota of patients with multiple sclerosis that are directly associated with blood biomarkers of inflammation, and in treatment-naïve cases bacterial richness is positively associated with disease activity. Yet, the finding of two symbiotic bacterial species in non-disease-active cases that produce favorable immune-modulating compounds provides a rationale for testing these bacteria as adjunct therapeutics in future clinical trials.https://doi.org/10.1186/s13073-022-01148-1Multiple sclerosisShotgun sequencingGut microbiotaGordonibacter urolithinfaciensFaecalibacterium prausnitzii |
| spellingShingle | Florence Thirion Finn Sellebjerg Yong Fan Liwei Lyu Tue H. Hansen Nicolas Pons Florence Levenez Benoit Quinquis Evelina Stankevic Helle B. Søndergaard Thomas M. Dantoft Casper S. Poulsen Sofia K. Forslund Henrik Vestergaard Torben Hansen Susanne Brix Annette Oturai Per Soelberg Sørensen Stanislav D. Ehrlich Oluf Pedersen The gut microbiota in multiple sclerosis varies with disease activity Genome Medicine Multiple sclerosis Shotgun sequencing Gut microbiota Gordonibacter urolithinfaciens Faecalibacterium prausnitzii |
| title | The gut microbiota in multiple sclerosis varies with disease activity |
| title_full | The gut microbiota in multiple sclerosis varies with disease activity |
| title_fullStr | The gut microbiota in multiple sclerosis varies with disease activity |
| title_full_unstemmed | The gut microbiota in multiple sclerosis varies with disease activity |
| title_short | The gut microbiota in multiple sclerosis varies with disease activity |
| title_sort | gut microbiota in multiple sclerosis varies with disease activity |
| topic | Multiple sclerosis Shotgun sequencing Gut microbiota Gordonibacter urolithinfaciens Faecalibacterium prausnitzii |
| url | https://doi.org/10.1186/s13073-022-01148-1 |
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