A Commercial Probiotic Induces Tolerogenic and Reduces Pathogenic Responses in Experimental Autoimmune Encephalomyelitis

被引:39
作者
Calvo-Barreiro, Laura [1 ,2 ,3 ]
Eixarch, Herena [1 ,2 ,3 ]
Ponce-Alonso, Manuel [4 ,5 ]
Castillo, Mireia [1 ,2 ,3 ]
Lebron-Galan, Rafael [3 ,6 ]
Mestre, Leyre [3 ,7 ]
Guaza, Carmen [3 ,7 ]
Clemente, Diego [3 ,6 ]
del Campo, Rosa [4 ,5 ]
Montalban, Xavier [1 ,2 ,3 ,8 ]
Espejo, Carmen [1 ,2 ,3 ]
机构
[1] Hosp Univ Vall dHebron, Serv Neurol Neuroimmunol, Ctr Esclerosi Multiple Catalunya, Vall dHebron Inst Recerca, Passeig Vall dHebron 119-129, Barcelona 08035, Spain
[2] Univ Autonoma Barcelona, Bellaterra 08193, Cerdanyola Del, Spain
[3] Inst Salud Carlos III, Red Espanola Esclerosis Multiple REEM, Fondo Invest Sanitaria, Minist Econ & Competitividad, Madrid 28801, Spain
[4] Hosp Univ Ramon y Cajal, Serv Microbiol, Carretera Colmenar Km 9-1, Madrid 28034, Spain
[5] Inst Ramon y Cajal Invest Sanitaria IRYCIS, Carretera Colmenar Km 9-1, Madrid 28034, Spain
[6] Hosp Nacl Paraplej, Grp Neuroinmunoreparac, Unidad Invest, Finca La Peraleda S-N, Toledo 45071, Spain
[7] CSIC, Grp Neuroinmunol, Dept Neurobiol Func & Sistemas, Inst Cajal, Ave Doctor Arce 37, Madrid 28002, Spain
[8] Univ Toronto, Div Neurol, St Michaels Hosp, 30 Bond St, Toronto, ON M5B 1W8, Canada
关键词
gut microbiota; probiotics; immune regulation; experimental autoimmune encephalomyelitis; multiple sclerosis; adaptive immunity; antigen presenting cells; gut microbiome; gut permeability; REGULATORY T-CELLS; MULTIPLE-SCLEROSIS; DENDRITIC CELLS; PD-1; MICROBIOTA; MODEL; CNS; PUBLICATION; EXPRESSION; GUIDELINES;
D O I
10.3390/cells9040906
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Previous studies in experimental autoimmune encephalomyelitis (EAE) models have shown that some probiotic bacteria beneficially impact the development of this experimental disease. Here, we tested the therapeutic effect of two commercial multispecies probiotics-Lactibiane iki and Vivomixx-on the clinical outcome of established EAE. Lactibiane iki improves EAE clinical outcome in a dose-dependent manner and decreases central nervous system (CNS) demyelination and inflammation. This clinical improvement is related to the inhibition of pro-inflammatory and the stimulation of immunoregulatory mechanisms in the periphery. Moreover, both probiotics modulate the number and phenotype of dendritic cells (DCs). Specifically, Lactibiane iki promotes an immature, tolerogenic phenotype of DCs that can directly induce immune tolerance in the periphery, while Vivomixx decreases the percentage of DCs expressing co-stimulatory molecules. Finally, gut microbiome analysis reveals an altered microbiome composition related to clinical condition and disease progression. This is the first preclinical assay that demonstrates that a commercial probiotic performs a beneficial and dose-dependent effect in EAE mice and one of the few that demonstrates a therapeutic effect once the experimental disease is established. Because this probiotic is already available for clinical trials, further studies are being planned to explore its therapeutic potential in multiple sclerosis patients.
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页数:22
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