Manipulation of gut microbiota influences immune responses, axon preservation, and motor disability in a model of progressive multiple sclerosis
Mestre, Leyre (Red Española de Esclerosis Múltiple (REEM))
Carrillo-Salinas, Francisco J. (Instituto Cajal (Consejo Superior de Investigaciones Científicas))
Mecha, Miriam (Red Española de Esclerosis Múltiple (REEM))
Feliú, Ana (Red Española de Esclerosis Múltiple (REEM))
Espejo, Carmen (Hospital Universitari Vall d'Hebron)
Alvarez-Cermeño, José C. (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Villar, L. M. (Instituto Ramón y Cajal de Investigación Sanitaria (Madrid))
Guaza, Carmen (Red Española de Esclerosis Múltiple (REEM))

Data:	2019
Resum:	Gut microbiota dysbiosis has been implicated in MS and other immune diseases, although it remains unclear how manipulating the gut microbiota may affect the disease course. Using a well-established model of progressive MS triggered by intracranial infection with Theiler's murine encephalomyelitis virus (TMEV), we sought to determine whether dysbiosis induced by oral antibiotics (ABX) administered on pre-symptomatic and symptomatic phases of the disease influences its course. We also addressed the effects of microbiota recolonization after ABX withdrawn in the presence or absence of probiotics. Central and peripheral immunity, plasma acetate and butyrate levels, axon damage and motor disability were evaluated. The cocktail of ABX prevented motor dysfunction and limited axon damage in mice, which had fewer CD4 and CD8 T cells in the CNS, while gut microbiota recolonization worsened motor function and axonal integrity. The underlying mechanisms of ABX protective effects seem to involve CD4CD39 T cells and CD5CD1d B cells into the CNS. In addition, microglia adopted a round amoeboid morphology associated to an anti-inflammatory gene profile in the spinal cord of TMEV mice administered ABX. The immune changes in the spleen and mesenteric lymph nodes were modest, yet ABX treatment of mice limited IL-17 production ex vivo. Collectively, our results provide evidence of the functional relevance of gut microbiota manipulation on the neurodegenerative state and disease severity in a model of progressive MS and reinforce the role of gut microbiota as target for MS treatment.
Ajuts:	Agencia Estatal de Investigación SAF2016-76449-R
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:	Theiler's virus model ; Gut microbiota ; Treg and Breg cells ; Neuroinflammation ; Multiple sclerosis
Publicat a:	Frontiers in immunology, Vol. 10 Núm. JUN (2019) , p. 1374, ISSN 1664-3224

DOI: 10.3389/fimmu.2019.01374
PMID: 31258540

18 p, 3.0 MB

El registre apareix a les col·leccions:
Articles > Articles de recerca
Articles > Articles publicats