Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Front Immunol. 2019 Jul 23;10:1662. doi: 10.3389/fimmu.2019.01662. eCollection 2019.
Gut microbiota has been proposed as an important environmental factor which can intervene and modulate central nervous system autoimmunity. Here, we altered the composition of gut flora with and norfloxacin in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We found that appropriate (5.0 × 10 CFU/mL intragastrically daily, staring at weaning period of age) and norfloxacin (5 mg/kg intragastrically daily, 1 week prior to EAE induction) treatment could both ameliorate EAE although there are obvious differences in gut microbiota composition between these two interventions. increased while norfloxacin decreased the abundance and diversity of the gut microbiota in EAE mice, and both of the treatments decreased / ratio. In the genus level, treatment increased the abundance of while and increased in norfloxacin treatment. Moreover, both interventions reduced and species. Although there was discrepancy in the gut microbiota composition with the two interventions, and norfloxacin treatment both reduced Th17 response and increased Treg response in the gastrointestinal tract and extra-gastrointestinal organ systems in EAE mice. And the reduced activity of p38 mitogen-activated kinase and c-Jun N-terminal kinase signaling in spinal cord could be observed in the two interventions. The results suggested that manipulation of gut microbiota interventions should take factors such as timing, duration, and dosage into consideration. The discrepancy in the gut microbiota composition and the similar protective T cells response of and norfloxacin implies that achieving intestinal microecology balance by promoting and/or inhibiting the gut microbiota contribute to the well-being of immune response in EAE mice.
肠道微生物群被认为是一种重要的环境因素，它可以干预和调节中枢神经系统自身免疫。在这里，我们用万古霉素和诺氟沙星改变实验性自身免疫性脑脊髓炎（EAE），即多发性硬化症的动物模型中的肠道菌群组成。我们发现，适当的万古霉素（每天 5.0×10 CFU/mL 灌胃，从断奶期开始）和诺氟沙星（每天 5mg/kg 灌胃，在 EAE 诱导前 1 周）治疗都可以改善 EAE，尽管这两种干预措施在肠道微生物群组成上存在明显差异。万古霉素治疗增加了 EAE 小鼠肠道微生物群的丰度和多样性，而诺氟沙星治疗则降低了其丰度和多样性，且这两种治疗都降低了/比值。在属水平上，万古霉素治疗增加了的丰度，而诺氟沙星治疗则增加了和的丰度。此外，这两种干预措施都减少了和的种类。尽管这两种干预措施在肠道微生物群组成上存在差异，但万古霉素和诺氟沙星治疗都减少了 EAE 小鼠胃肠道和胃肠道外器官系统中的 Th17 反应，增加了 Treg 反应。并且可以观察到这两种干预措施都降低了脊髓中 p38 丝裂原活化蛋白激酶和 c-Jun N 末端激酶信号的活性。这些结果表明，肠道微生物群干预措施的操作应该考虑到时间、持续时间和剂量等因素。万古霉素和诺氟沙星在肠道微生物群组成上的差异和相似的保护性 T 细胞反应表明，通过促进和/或抑制肠道微生物群来实现肠道微生态平衡有助于 EAE 小鼠的免疫反应健康。
