How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process.
How oral probiotics affect the severity of an experimental model of progressive multiple sclerosis? Bringing commensal bacteria into the neurodegenerative process.
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DOI：
10.1080/19490976.2020.1813532
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发表时间：
2020-11-09
期刊：
影响因子：
12.2
通讯作者：
Guaza C
中科院分区：
文献类型：
--
作者：
Mestre L;Carrillo-Salinas FJ;Feliú A;Mecha M;Alonso G;Espejo C;Calvo-Barreiro L;Luque-García JL;Estevez H;Villar LM;Guaza C
越来越多的研究支持肠道微生物群、免疫系统和中枢神经系统之间的双向相互作用与多发性硬化症的病理生理学相关。多项研究报告了多发性硬化症患者肠道微生物组的变化。此外，对多发性硬化症动物模型的各种研究表明，肠道共生微生物群的特定成员可以加剧或减轻神经炎症。益生菌代表口服无毒免疫调节剂，与当前的多发性硬化症治疗结合使用时将发挥益处。在这里，我们研究了 Vivomixx 对原发性进行性多发性硬化症小鼠模型中肠道微生物组以及中枢和外周免疫反应的影响。 Vivomixx 给药与许多类群的丰度增加相关，例如拟杆菌门、放线菌门、特内里古特门和 TM7。与此同时，感染泰勒病毒的小鼠的运动障碍也明显改善。在中枢神经系统中，Vivomixx 减少了小胶质细胞增生、星形胶质细胞增生和白细胞浸润。值得注意的是，Vivomixx 增强了 CNS 中 Breg 细胞 (CD19+CD5+CD1dhigh) 的存在，虽然 IL-1β 和 IL-6 的脊髓基因表达减少，但益生菌促进了 IL-10 基因表达。最重要的发现之一是接受 Vivomixx 治疗的 TMEV 小鼠血浆中丁酸盐和乙酸盐水平升高。外周免疫学变化是微妙的，但有趣的是，益生菌限制了从感染泰勒病毒的小鼠肠系膜淋巴结中纯化的 Th17 极化 CD4+ T 细胞产生 IL-17。我们的数据强化了口服益生菌的有益作用，口服益生菌将成为当前多发性硬化症疗法的辅助治疗。
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.
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影响因子：
16.6
作者：
Jangi S;Gandhi R;Cox LM;Li N;von Glehn F;Yan R;Patel B;Mazzola MA;Liu S;Glanz BL;Cook S;Tankou S;Stuart F;Melo K;Nejad P;Smith K;Topçuolu BD;Holden J;Kivisäkk P;Chitnis T;De Jager PL;Quintana FJ;Gerber GK;Bry L;Weiner HL
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影响因子：
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作者：
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6.3
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影响因子：
3.7
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影响因子：
7.3
作者：
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