Administration of bifidobacterium and lactobacillus strains modulates experimental myasthenia gravis and experimental encephalomyelitis in Lewis rats

Consonni, Alessandra; Cordiglieri, Chiara; Rinaldi, Elena; Marolda, Roberta; Ravanelli, Ilaria; Guidesi, Elena; Elli, Marina; Mantegazza, Renato; Baggi, Fulvio

doi:10.18632/oncotarget.25170

Cited by 38 publications

(63 citation statements)

References 86 publications

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“…We observed that the therapeutic treatment with BBmix was associated with increased FoxP3 and TGFβ mRNAs expression in drLNs of EAMG animals (Figure 2A). This observation is in line with our previous report on the efficacy of preventive probiotic treatment in this model (6); overall, these data further support the hypothesis of TGFβ as systemic cytokine able to orchestrate the immune-modulation activated by probiotics (6), besides FoxP3 + cells as key players in probiotic induced-suppressive activity (43,44).…”

Section: Discussionsupporting

confidence: 92%

“…Over the past years, many studies have been conducted and demonstrated the benefits of probiotic treatment in animal models of inflammatory diseases, such as experimental arthritis (3), experimentally induced colitis (4) and experimental autoimmune encephalomyelitis (5). Effects of probiotic administration on clinical symptoms and on immune mechanisms of EAMG has been investigated by us and other groups, according to a preventive or prophylactic/preventive protocol (6,7). We previously demonstrated the effects of the preventive administration of two bifidobacteria strains or two lactobacilli strains in the Lewis rats EAMG model.…”

Section: Introductionmentioning

confidence: 99%

“…We observed that probiotics significantly attenuated EAMG symptoms, decreased serum anti-rat AChR antibody levels and increased muscle AChR content. Pro-inflammatory and immunoregulatory transcripts were found differentially expressed in primary and secondary immune organs, and increased levels of Transforming Growth Factor-β (TGFβ) were measured in EAMG rat serum (6).…”

Section: Introductionmentioning

confidence: 99%

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Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

et al. 2019

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Beneficial effects of probiotics on gut microbiota homeostasis and inflammatory immune responses suggested the investigation of their potential clinical efficacy in experimental models of autoimmune diseases. Indeed, administration of two bifidobacteria and lactobacilli probiotic strains prevented disease manifestations in the Lewis rat model of Myasthenia Gravis (EAMG). Here, we demonstrate the clinical efficacy of therapeutic administration of vital bifidobacteria (i.e., from EAMG onset). The mechanisms involved in immunomodulation were investigated with ex vivo and in vitro experiments. Improvement of EAMG symptoms was associated to decreased anti-rat AChR antibody levels, and differential expression of TGFβ and FoxP3 immunoregulatory transcripts in draining lymph nodes and spleen of treated-EAMG rats. Exposure of rat bone marrow-derived dendritic cells to bifidobacteria or lactobacilli strains upregulated toll-like receptor 2 mRNA expression, a key molecule involved in bacterium recognition via lipotheicoic acid. Live imaging experiments of AChR-specific effector T cells, co-cultured with BMDCs pre-exposed to bifidobacteria, demonstrated increased percentages of motile effector T cells, suggesting a hindered formation of TCR-peptide-MHC complex. Composition of gut microbiota was studied by 16S rRNA gene sequencing, and α and β diversity were determined in probiotic treated EAMG rats, with altered ratios between Tenericutes and Verrucomicrobia (phylum level), and Ruminococcaceae and Lachnospiraceae (family level). Moreover, the relative abundance of Akkermansia genus was found increased compared to healthy and probiotic treated EAMG rats. In conclusion, our findings confirms that the administration of vital bifidobacteria at EAMG onset has beneficial effects on disease progression; this study further supports preclinical research in human MG to evaluate probiotic efficacy as supplementary therapy in MG.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

et al. 2019

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“…As previously mentioned, the family Lachnospiraceae has been previously associated with butyrate production and has also been correlated with IL-10 and TGF-β production by different immune cells [65]. Regarding Bifidobacteria, probiotics composed of different strains including Bifidobacterium have exhibited beneficial effects in EAE [11,69] and MS [17,18] and have been correlated with anti-inflammatory immune markers. Concerning Vivomixx, composed by genera Lactobacillus, Bifidobacterium, and Streptococcus, the observed increase in the genus Streptococcus (family Streptococcaceae) is consistent with probiotic composition, with prior studies in Vivomixx-treated MS patients, and connected to anti-inflammatory responses affecting mainly DCs and monocytes [17,18].…”

Section: Discussionmentioning

confidence: 85%

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

Calvo-Barreiro

Eixarch

Ponce-Alonso

et al. 2020

Cells

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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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“…One of the safe and appropriate ways to modulate T cells in MS is to orally administer specific autoantigens [13,14]. Administration of Bifidobacteria or Lactobacteria probiotic strains to mice has been shown to increase Treg cells and tumor growth factor (TGF)-β levels and reduce the severity of EAE clinical symptoms, in parallel with improvement in the regeneration of myelin in the spinal cord compared to the control [15,16]. Administration of both Bifidobacteria and Lactobacteria strains induce an additional significant delay in the onset of EAE and related clinical symptoms, together with a substantial reduction of mononuclear infiltration into the CNS, and increased level of Treg cells of the CD4 + CD25 + Foxp3 + phenotype in mouse spleen and lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice

Dargahi

Matsoukas²,

Apostolopoulos

2020

Brain Sciences

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Probiotic bacteria have beneficial effects to the development and maintenance of a healthy microflora that subsequently has health benefits to humans. Some of the health benefits attributed to probiotics have been noted to be via their immune modulatory properties suppressing inflammatory conditions. Hence, probiotics have become prominent in recent years of investigation with regard to their health benefits. As such, in the current study, we determined the effects of Streptococcus thermophilus to agonist MBP83–99 peptide immunized mouse spleen cells. It was noted that Streptococcus thermophilus induced a significant increase in the expression of anti-inflammatory IL-4, IL-5, IL-10 cytokines, and decreased the secretion of pro-inflammatory IL-1β and IFN-γ. Regular consumption of Streptococcus thermophilus may therefore be beneficial in the management and treatment of autoimmune diseases such as multiple sclerosis.

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Administration of bifidobacterium and lactobacillus strains modulates experimental myasthenia gravis and experimental encephalomyelitis in Lewis rats

Cited by 38 publications

References 86 publications

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

Therapeutic Effect of Bifidobacterium Administration on Experimental Autoimmune Myasthenia Gravis in Lewis Rats

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

Streptococcus thermophilus ST285 Alters Pro-Inflammatory to Anti-Inflammatory Cytokine Secretion against Multiple Sclerosis Peptide in Mice

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