Multiple Sclerosis Group, Neuroscience Area, Biodonostia Research Institute, San Sebastian 20014, Spain.
Center for Cooperative Research in Biomaterials (CIC biomaGUNE), Basque Research and Technology Alliance (BRTA), Paseo Miramón 182, Donostia, San Sebastián 20014, Spain.
ACS Chem Neurosci. 2021 Mar 3;12(5):893-905. doi: 10.1021/acschemneuro.0c00695. Epub 2021 Feb 10.
Multiple sclerosis (MS) is a chronic and neurodegenerative disease of the central nervous system (CNS) characterized by the immune mediated attack on axons and the subsequent demyelination. There is growing evidence that the gut microbiota of MS patients is altered; however, the connection between demyelination events and changes in the gut microbiota has not been determined. The objective of the current work was to characterize the microbial dysbiosis in two murine demyelinating models and to study the correlation between them. Concurrently, their suitability as predictors of microbial changes in MS patients was assessed. To this purpose, experimental autoimmune encephalomyelitis (EAE) and cuprizone (CPZ) models were induced in C57BL/6 mice that were monitored for 4 and 9 weeks, respectively. Fecal samples were collected during disease progression. Motor skill performance was evaluated by EAE scale measurement in EAE mice and demyelination by magnetic resonance imaging (MRI) in CPZ ones. EAE and CPZ mice revealed drastic microbial changes according to disease progression, adding a new layer of complexity to the understanding of demyelination and remyelination processes. Besides, the reported microbial changes replicate most of the characteristics that define the potential dysbiosis in MS patients. The controlled environment and stable diet that animals have in research centers offer an exceptional scenario to modify animal's microbiota and provide opportunities to study host microbiota interplay with restrained conditions not achievable in human studies. Nevertheless the slight differences from murine model's and patient's microbiota should be considered in the design of studies aiming to modulate the microbiota.
多发性硬化症（MS）是一种中枢神经系统（CNS）的慢性神经退行性疾病，其特征是免疫介导的轴突攻击和随后的脱髓鞘。越来越多的证据表明，MS 患者的肠道微生物群发生了改变；然而，脱髓鞘事件与肠道微生物群变化之间的联系尚未确定。目前工作的目的是描述两种实验性自身免疫性脑脊髓炎（EAE）和 CPZ 模型的微生物失调，并研究它们之间的相关性。同时，评估它们作为 MS 患者微生物变化预测因子的适用性。为此，在 C57BL/6 小鼠中诱导实验性自身免疫性脑脊髓炎（EAE）和 CPZ 模型，并分别监测 4 周和 9 周。在疾病进展过程中收集粪便样本。通过 EAE 小鼠的 EAE 量表测量和 CPZ 小鼠的磁共振成像（MRI）评估运动技能表现。EAE 和 CPZ 小鼠根据疾病进展显示出明显的微生物变化，为脱髓鞘和髓鞘再生过程的理解增添了新的复杂性。此外，报告的微生物变化复制了大多数定义 MS 患者潜在失调的特征。研究中心中动物的受控环境和稳定饮食为改变动物的微生物群提供了一个极好的场景，并提供了在人类研究中无法实现的受限条件下研究宿主微生物群相互作用的机会。然而，在设计旨在调节微生物群的研究时，应该考虑到与小鼠模型和患者微生物群的微小差异。
