A Commercial Probiotic Induces Tolerogenic and Reduces Pathogenic Responses in Experimental Autoimmune Encephalomyelitis.
Laura Calvo-BarreiroHerena EixarchManuel Ponce-AlonsoMireia CastilloRafael Lebrón-GalánLeyre MestreCarmen GuazaDiego ClementeRosa Del CampoXavier MontalbanCarmen EspejoPublished in: Cells (2020)
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.
Keyphrases
- dendritic cells
- multiple sclerosis
- clinical trial
- regulatory t cells
- bacillus subtilis
- end stage renal disease
- immune response
- ejection fraction
- oxidative stress
- newly diagnosed
- chronic kidney disease
- lactic acid
- type diabetes
- stem cells
- bone marrow
- metabolic syndrome
- adipose tissue
- patient reported outcomes
- mesenchymal stem cells
- skeletal muscle
- case control
- insulin resistance
- cell therapy
- study protocol
- double blind
- phase iii