Selected Clostridia Strains from The Human Microbiota and their Metabolite, Butyrate, Improve Experimental Autoimmune Encephalomyelitis
Autor: | Leyre Mestre, Carmen Espejo, Xavier Montalban, Juan José González-López, Takeshi Tanoue, Herena Eixarch, Thais Cornejo, Laura Calvo-Barreiro, Kenya Honda, Carmen Guaza, Mireia Castillo, Carme Martínez Costa, María del Carmen Martínez-Cuesta |
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Přispěvatelé: | Instituto de Salud Carlos III, European Commission, Generalitat de Catalunya |
Rok vydání: | 2021 |
Předmět: |
Experimental Autoimmune Encephalomyelitis
Encephalomyelitis Autoimmune Experimental Clostridiaceae Short-chain Fatty Acid Butyrate Gut flora T-Lymphocytes Regulatory Clostridia Immune Regulation Multiple sclerosis Mice Immune system medicine Animals Humans Pharmacology (medical) Gut Microbiota Pharmacology Microglia biology Experimental autoimmune encephalomyelitis Human microbiome Clostridia Strains Fatty Acids Volatile medicine.disease biology.organism_classification Gastrointestinal Microbiome Mice Inbred C57BL Butyrates medicine.anatomical_structure Immunology Dysbiosis Original Article Female Neurology (clinical) |
Zdroj: | Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona Digital.CSIC. Repositorio Institucional del CSIC instname Neurotherapeutics |
Popis: | Gut microbiome studies in multiple sclerosis (MS) patients are unravelling some consistent but modest patterns of gut dysbiosis. Among these, a significant decrease of Clostridia cluster IV and XIVa has been reported. In the present study, we investigated the therapeutic effect of a previously selected mixture of human gut-derived 17 Clostridia strains, which belong to Clostridia clusters IV, XIVa, and XVIII, on the clinical outcome of experimental autoimmune encephalomyelitis (EAE). The observed clinical improvement was related to lower demyelination and astrocyte reactivity as well as a tendency to lower microglia reactivity/infiltrating macrophages and axonal damage in the central nervous system (CNS), and to an enhanced immunoregulatory response of regulatory T cells in the periphery. Transcriptome studies also highlighted increased antiinflammatory responses related to interferon beta in the periphery and lower immune responses in the CNS. Since Clostridia-treated mice were found to present higher levels of the immunomodulatory short-chain fatty acid (SCFA) butyrate in the serum, we studied if this clinical effect could be reproduced by butyrate administration alone. Further EAE experiments proved its preventive but slight therapeutic impact on CNS autoimmunity. Thus, this smaller therapeutic effect highlighted that the Clostridia-induced clinical effect was not exclusively related to the SCFA and could not be reproduced by butyrate administration alone. Although it is still unknown if these Clostridia strains will have the same effect on MS patients, gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a beneficial effect on MS clinical course. This work was supported by the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, co-funded by the European Union (European Regional Development Fund/European Social Fund) “A way to build Europe” under Grant PI15/00840 and RD16/0015/004; and “Agència de Gestió d’Ajuts Universitaris i de Recerca” (AGAUR; Generalitat de Catalunya) under Grant 2017SGR527. |
Databáze: | OpenAIRE |
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