Selected Clostridia Strains from The Human Microbiota and their Metabolite, Butyrate, Improve Experimental Autoimmune Encephalomyelitis
Calvo-Barreiro, Laura (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Eixarch, Herena (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Cornejo-Sánchez, Thais (Hospital Universitari Vall d'Hebron)
Costa, Carme (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Castillo, Mireia (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Mestre, Leyre (Instituto Cajal (Consejo Superior de Investigaciones Científicas))
Guaza, Carmen (Instituto Cajal (Consejo Superior de Investigaciones Científicas))
Martínez-Cuesta, María del Carmen (Consejo Superior de Investigaciones Científicas (Espanya). Instituto de Investigación en Ciencias de la Alimentación)
Tanoue, Takeshi (RIKEN Center for Integrative Medical Sciences)
Honda, Kenya (RIKEN Center for Integrative Medical Sciences)
González-López, Juanjo (Hospital Universitari Vall d'Hebron)
Montalban, Xavier (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Espejo, Carmen (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	Gut microbiome studies in multiple sclerosis (MS) patients are unravelling some consistent but modest patterns of gut dysbiosis. Among these, a signifcant decrease of Clostridia cluster IV and XIVa has been reported. In the present study, we investigated the therapeutic efect 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/infltrating 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 antiinfammatory 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 efect could be reproduced by butyrate administration alone. Further EAE experiments proved its preventive but slight therapeutic impact on CNS autoimmunity. Thus, this smaller therapeutic efect highlighted that the Clostridia-induced clinical efect 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 efect on MS patients, gut dysbiosis in MS patients could be partially rebalanced by these commensal bacteria and their immunoregulatory properties could have a benefcial efect on MS clinical course.
Ajuts:	Instituto de Salud Carlos III RD16/0015/004 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR527
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Gut Microbiota ; Clostridia Strains ; Short-chain Fatty Acid ; Immune Regulation ; Experimental Autoimmune Encephalomyelitis ; Multiple sclerosis
Publicat a:	Neurotherapeutics, Vol. 18 (april 2021) , p. 920-937, ISSN 1878-7479

DOI: 10.1007/s13311-021-01016-7
PMID: 33829410

18 p, 6.7 MB

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