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

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

doi:10.18632/oncotarget.25170

Alessandra Consonni, Renato Mantegazza + Show 7 more

Open Access

https://doi.org/10.18632/oncotarget.25170

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Journal: Oncotarget	Publication Date: Apr 27, 2018
Citations: 34	License type: cc-by

Affiliation: Istituto Neurologico Carlo Besta

Abstract

Probiotics beneficial effects on the host are associated with regulation of the intestinal microbial homeostasis and with modulation of inflammatory immune responses in the gut and in periphery. In this study, we investigated the clinical efficacy of two lactobacillus and two bifidobacterium probiotic strains in experimental autoimmune myasthenia gravis (EAMG) and experimental autoimmune encephalomyelitis (EAE) models, induced in Lewis rats. Treatment with probiotics led to less severe disease manifestation in both models; ex vivo analyses showed preservation of neuromuscular junction in EAMG and myelin content in EAE spinal cord. Immunoregulatory transcripts were found differentially expressed in gut associated lymphoid tissue and in peripheral immunocompetent organs. Feeding EAMG animals with probiotics resulted in increased levels of Transforming Growth Factor-β (TGFβ) in serum, and increased percentages of regulatory T cells (Treg) in peripheral blood leukocyte. Exposure of immature dendritic cells to probiotics induced their maturation toward an immunomodulatory phenotype, and secretion of TGFβ. Our data showed that bifidobacteria and lactobacilli treatment effectively modulates disease symptoms in EAMG and EAE models, and support further investigations to evaluate their use in autoimmune diseases.

Highlights

In the recent years, there has been increasing interest on the role of the intestinal microbiota in health and disease, as well as on the use of probiotics to modulate its activity [1,2,3]
Lactobacilli and bifidobacteria ameliorate experimental autoimmune myasthenia gravis Torpedo californica acetylcholine receptor (AChR) (TAChR)-immunized Lewis rats were treated with combinations of lactobacilli (LC+Lactobacillus rhamnosus ATCC 53103 (LR)) or bifidobacteria (BB+BL), (Figure 1A); probiotic treatments were given in correspondence of the acute IgM-mediated and the chronic IgG-mediated phases, characteristic of the rat EAMG model
TAChR proliferative responses from draining lymph node cells (LNCs) were found not modified in LC+LR and in BB+BL treated EAMG rats compared to vehicle-fed group (Figure 1E)

Summary

Introduction

There has been increasing interest on the role of the intestinal microbiota in health and disease, as well as on the use of probiotics to modulate its activity [1,2,3]. Nutritional and energetic levels are monitored thanks to the gut microbiota, which conveys information from the ingested aliments (i.e., vitamins, minerals, carbohydrates, fats, etc.) to the CNS via the gut–brain axis; specific neurological pathways have evolved to respond to microbial commensals of the gut, either directly via microbial metabolites or indirectly by the immune, metabolic, or endocrine systems. Commensal bacteria in the gut are often the source of probiotic strains, and two common general benefits are associated with probiotics: supporting a healthy digestive www.oncotarget.com tract and a healthy immune system [9]. Probiotic treatment can promote the induction or restoration of regulatory-type immune responses [10,11,12], by modulating the balance between pro- and anti-inflammatory cytokines [13,14,15], enhancing the generation of IL10+, TGFβ+ and COX2+ regulatory DCs [16], and enriching CD4+CD25+ regulatory T cell (Treg) cells [17, 18]

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