Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice
Gut microbiota from multiple sclerosis patients enables spontaneous autoimmune encephalomyelitis in mice
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DOI：
10.1073/pnas.1711233114
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发表时间：
2017-10-03
影响因子：
11.1
通讯作者：
Wekerle, Hartmut
中科院分区：
文献类型：
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作者：
Berer, Kerstin;Gerdes, Lisa Ann;Wekerle, Hartmut
有新的证据表明，肠道微生物群在多发性硬化症（MS）的发病机制中起作用，多发性硬化症是一种公认的CNS自身免疫性疾病。在这里，我们比较了34个单卵双胞胎对MS不一致的肠道微生物组成。虽然整体微生物谱没有重大差异，但我们发现一些分类群（如Akkermansia）在未经处理的MS双胞胎中显著增加。此外，最值得注意的是，当移植到自发脑自身免疫的转基因小鼠模型时，MS双胞胎衍生的微生物群诱导的自身免疫发生率显著高于健康双胞胎衍生的微生物群。定殖小鼠的微生物谱显示出高的个体内和显著的时间稳定性，具有几个差异，包括Sutterella，一种在体外诱导保护性免疫调节谱的生物体。来自MS双胞胎样本的小鼠受体的免疫细胞产生的IL-10比来自健康双胞胎样本定殖的小鼠的免疫细胞少。IL-10可能在自发性CNS自身免疫中具有调节作用，因为用健康双胞胎粪便样本定殖的小鼠中的细胞因子的中和增加了疾病发生率。这些发现提供了证据，证明MS衍生的微生物群含有在转基因小鼠模型中沉淀MS样自身免疫性疾病的因子。因此，他们鼓励详细寻找人类MS中的保护性和致病性微生物成分。
There is emerging evidence that the commensal microbiota has a role in the pathogenesis of multiple sclerosis ( MS), a putative autoimmune disease of the CNS. Here, we compared the gut microbial composition of 34 monozygotic twin pairs discordant for MS. While there were no major differences in the overall microbial profiles, we found a significant increase in some taxa such as Akkermansia in untreated MS twins. Furthermore, most notably, when transplanted to a transgenic mouse model of spontaneous brain autoimmunity, MS twin-derived microbiota induced a significantly higher incidence of autoimmunity than the healthy twin-derived microbiota. The microbial profiles of the colonized mice showed a high intraindividual and remarkable temporal stability with several differences, including Sutterella, an organism shown to induce a protective immunoregulatory profile in vitro. Immune cells from mouse recipients of MS-twin samples produced less IL-10 than immune cells from mice colonized with healthy-twin samples. IL-10 may have a regulatory role in spontaneous CNS autoimmunity, as neutralization of the cytokine in mice colonized with healthy-twin fecal samples increased disease incidence. These findings provide evidence that MS-derived microbiota contain factors that precipitate an MS-like autoimmune disease in a transgenic mouse model. They hence encourage the detailed search for protective and pathogenic microbial components in human MS.