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

Laura Calvo-Barreiro,Mireia Castillo,Carmen Guaza,Carmen Espejo,Diego Clemente,Rosa Del Campo,Herena Eixarch,Xavier Montalban,Leyre Mestre,Manuel Ponce-Alonso,Rafael Lebrón-Galán

doi:10.3390/cells9040906

Abstract

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.

Highlights

Multiple sclerosis (MS) is a chronic, degenerative autoimmune disease and the most common inflammatory demyelinating disorder of the central nervous system (CNS) worldwide [1]
Whereas treatment with Lactibiane iki improved the clinical outcome (area under the curve (AUC): 72.60 ± 18.12, n = 20, p = 0.029) compared to vehicle treatment (AUC: 83.88 ± 8.48, n = 18), Vivomixx treatment did not ameliorated the clinical course of already established EAE (AUC: 75.35 ± 18.73, n = 20, p = 0.100) (Figure 1a,b)
We observed greater clinical improvement in mice treated with Lactibiane iki (AUC: 62.78 ± 23.63, n = 17, p = 0.008) than in vehicle-treated mice (AUC: 80.57 ± 10.82, n = 17), but still, Vivomixx treatment did not reach statistical significance (AUC: 69.47 ± 20.49, n = 17, p = 0.057)

Summary

Introduction

Multiple sclerosis (MS) is a chronic, degenerative autoimmune disease and the most common inflammatory demyelinating disorder of the central nervous system (CNS) worldwide [1]. The aetiology of the disease is still unclear, MS could be triggered in the periphery by activated autoreactive immune cells that subsequently infiltrate into the CNS or by some CNS-intrinsic events [1] Both innate and adaptive immune responses participate in MS pathogenesis. The well-known defective function of regulatory T (Treg ) cells in MS patients [3] can partially explain the disease pathogenesis, since peripheral tolerance mechanisms are essential to prevent the self-reactivity of circulating autoreactive immune cells. Given this relationship, some therapeutic approaches try to skew pro-inflammatory responses towards enhancing anti-inflammatory (e.g., Th2 cells) or even immunoregulatory (e.g., Treg cells) populations to suppress autoreactive populations

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