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The role of gut microbiota in shaping the relapse-remitting and chronic-progressive forms of multiple sclerosis in mouse models

机译：肠道菌群在小鼠模型中塑造多发性硬化的复发缓解和慢性进展形式中的作用

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Using a mouse model of multiple sclerosis (MS), experimental autoimmune encephalitis (EAE), we evaluated the role of gut microbiota in modulating chronic-progressive (CP) versus relapse-remitting (RR) forms of the disease. We hypothesized that clinical courses of EAE may be shaped by differential gut microbiota. Metagenomic sequencing of prokaryotic 16S rRNA present in feces from naïve mice and those exhibiting CP-EAE or RR-EAE revealed significantly diverse microbial populations. Microbiota composition was considerably different between naïve strains of mice, suggesting microbial components present in homeostatic conditions may prime mice for divergent courses of disease. Additionally, there were differentially abundant bacteria in CP and RR forms of EAE, indicating a potential role for gut microbiota in shaping tolerant or remittance-favoring, and pathogenic or pro-inflammatory-promoting conditions. Furthermore, immunization to induce EAE led to significant alterations in gut microbiota, some were shared between disease courses and others were course-specific, supporting a role for gut microbial composition in EAE pathogenesis. Moreover, using Linear Discriminant Analysis (LDA) coupled with effect size measurement (LEfSe) to analyze microbial content, biomarkers of each naïve and disease states were identified. Our findings demonstrate for the first time that gut microbiota may determine the susceptibility to CP or RR forms of EAE.
机译：使用多发性硬化症（MS），实验性自身免疫性脑炎（EAE）的小鼠模型，我们评估了肠道菌群在调节疾病的慢性进展（CP）与复发缓解（RR）形式中的作用。我们假设，EAE的临床病程可能由肠道菌群的差异决定。来自幼稚小鼠和表现出CP-EAE或RR-EAE的小鼠粪便中存在的原核16S rRNA的元基因组测序揭示了微生物种群的多样性。幼稚小鼠品系之间的微生物群组成有很大不同，这表明在稳态条件下存在的微生物成分可能使小鼠引发疾病的不同进程。此外，EAE的CP和RR形式存在差异丰富的细菌，表明肠道菌群在塑造耐受性或汇款形成，致病性或促炎性疾病中具有潜在作用。此外，免疫诱导EAE导致肠道菌群发生显着变化，其中一些在病程之间共享，另一些则是病程特异性的，从而支持了肠道微生物组成在EAE发病机理中的作用。此外，使用线性判别分析（LDA）结合效应大小测量（LEfSe）来分析微生物含量，可以鉴定每种幼稚和疾病状态的生物标志物。我们的发现首次证明肠道菌群可能决定对EAE的CP或RR形式的敏感性。

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