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通过. 对肠道的定植来调节实验性自身免疫性脑脊髓炎

Modulation of experimental autoimmune encephalomyelitis through colonisation of the gut with .

机构信息

Department of Pathology, University of Utah School of Medicine, 15 North Medical Drive East, 2600 EEJMRB, Salt Lake City, UT 84112, USA.

Laboratory of Bacteriology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 2 Room 202, 903 4th Street, Hamilton, MT 59840, USA.

出版信息

Benef Microbes. 2020 Nov 15;11(7):669-684. doi: 10.3920/BM2020.0012. Epub 2020 Oct 13.

Abstract

Multiple sclerosis (MS) is a neuro-inflammatory autoimmune disease of the central nervous system (CNS) that affects young adults. It is characterised by the development of demyelinating lesions and inflammation within the CNS. Although the causes of MS are still elusive, recent work using patient samples and experimental animal models has demonstrated a strong relationship between the gut microbiota and its contribution to CNS inflammation and MS. While there is no cure for MS, alteration of the gut microbiota composition through the use of probiotics is a very promising treatment. However, while most recent works have focused on the use of probiotics to modify pre-existing disease, little is known about its role in protecting from the establishment of MS. In this study, we determined whether colonisation with the probiotic bacterium strain Nissle 1917 (EcN) could be used as a prophylactic strategy to prevent or alter the development of experimental autoimmune encephalomyelitis (EAE), a preclinical model of MS. We found that double gavage (two doses) of EcN before induction of EAE delayed disease onset and decreased disease severity. We also found that EcN-treated mice had decreased amounts of perivascular cuffing, CD4 T cell infiltration into the CNS, together with significantly decreased absolute numbers of Th1 cells, and reduced activation of microglia. Although further studies are necessary to comprehend the exact protective mechanisms induced, our study supports a promising use of EcN as a probiotic for the prevention of MS.

摘要

多发性硬化症(MS)是一种影响年轻人的中枢神经系统(CNS)的神经炎症性自身免疫性疾病。其特征是 CNS 内脱髓鞘病变和炎症的发展。尽管 MS 的病因仍不清楚,但使用患者样本和实验动物模型的最新研究表明,肠道微生物群与其对 CNS 炎症和 MS 的贡献之间存在很强的关系。虽然没有治愈 MS 的方法,但通过使用益生菌来改变肠道微生物群组成是一种很有前途的治疗方法。然而,虽然最近的大多数研究都集中在使用益生菌来改变已存在的疾病上,但对于其在预防 MS 发生中的作用知之甚少。在这项研究中,我们确定了是否可以使用益生菌菌株 Nissle 1917(EcN)定植作为预防策略来预防或改变实验性自身免疫性脑脊髓炎(EAE)的发展,EAE 是 MS 的临床前模型。我们发现,在 EAE 诱导前进行两次 EcN 灌胃(两次剂量)可延迟疾病发作并降低疾病严重程度。我们还发现,EcN 处理的小鼠血管周围套袖形成减少,CD4 T 细胞浸润到 CNS 减少,Th1 细胞绝对数量明显减少,小胶质细胞激活减少。尽管需要进一步研究来理解所诱导的确切保护机制,但我们的研究支持将 EcN 用作预防 MS 的益生菌。

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