How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process

Leyre Mestre,Francisco J Carrillo-Salinas,Ana Feliú,Miriam Mecha,Graciela Alonso,Carmen Espejo,Laura Calvo-Barreiro,José L Luque-García,Héctor Estevez,Luisa María Villar,Carmen Guaza

doi:10.1080/19490976.2020.1813532

Abstract

ABSTRACT A growing number of studies support that the bidirectional interactions between the gut microbiota, the immune system and the CNS are relevant for the pathophysiology of MS. Several studies have reported alterations in the gut microbiome of MS patients. In addition, a variety of studies in animal models of MS have suggested that specific members of the gut commensal microbiota can exacerbate or ameliorate neuroinflammation. Probiotics represent oral nontoxic immunomodulatory agents that would exert benefits when using in combination with current MS therapy. Here we investigate the effect of Vivomixx on the gut microbiome and central and peripheral immune responses in a murine model of primary progressive MS. Vivomixx administration was associated with increased abundance of many taxa such as Bacteroidetes, Actinobacteria, Tenericutes and TM7. This was accompanied by a clear improvement of the motor disability of Theiler’s virus infected mice; in the CNS Vivomixx reduced microgliosis, astrogliosis and leukocyte infiltration. Notably, the presence of Breg cells (CD19+CD5+CD1dhigh) in the CNS was enhanced by Vivomixx, and while spinal cord gene expression of IL-1β and IL-6 was diminished, the probiotic promoted IL-10 gene expression. One of the most significant findings was the increased plasma levels of butyrate and acetate levels in TMEV-mice that received Vivomixx. Peripheral immunological changes were subtle but interestingly, the probiotic restricted IL-17 production by Th17-polarized CD4+ T-cells purified from the mesenteric lymph nodes of Theiler’s virus infected mice. Our data reinforce the beneficial effects of oral probiotics that would be coadjuvant treatments to current MS therapies.

Highlights

The etiology of MS remains unknown, envir onmental and genetic risk factors are involved in the pathogenesis of the disease.[1]
We have studied the effect of administering the oral multi-strain probiotic, Vivomixx, on the gut microbiome and plasma short chain fatty acids (SCFAs) in the late chronic phase of a murine model of PPMS, the Theiler’s murine encephalomyelitis virus induced demyelinating disease (TMEVIDD)
We explored the effect of manipulating the gut microbiota by oral administration of Vivomixx dur ing the chronic phase of disease (Figure 1(a))

Summary

Introduction

The etiology of MS remains unknown, envir onmental and genetic risk factors are involved in the pathogenesis of the disease.[1]. Studies using the encephalomyelitis autoimmune experimental (EAE) model of MS described lower incidence in germ free (GF) or antibiotic treated mice than in specific pathogen free (SPF) mice,[6,7,8] while recolonization restored the susceptibility to develop EAE.[3] other studies reported a therapeutic role of probiotic administration in a variety of EAE models. On this matter, orally admin istration of Bacteroides fragilis,[9,10] Prevotella histicola,[11] different species of Lactobacillus

Methods

Results

Conclusion