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

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