Lactobacillus reuteri Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota

Lactobacillus reuteri Reduces the Severity of Experimental Autoimmune Encephalomyelitis in Mice by Modulating Gut Microbiota
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DOI:
10.3389/fimmu.2019.00385
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发表时间:
2019-03-07
影响因子:
7.3
通讯作者:
Liu, Yuying
Liu, Yuying
中科院分区:
医学2区
文献类型:
--
作者:
He, Baokun;Hoang, Thomas K.;Liu, Yuying

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肠道微生物组在免疫功能中起着重要作用,并与多发性硬化症(MS)有关。然而,微生物群的调节如何以及是否可以预防或治疗MS在很大程度上仍然未知。在这项研究中,我们表明益生菌罗伊氏乳杆菌DSM 17938(L。reuten)改善了鼠实验性自身免疫性脑脊髓炎(EAE)的发展,EAE是广泛使用的MS动物模型,该模型主要由T(H)17和T(H)1细胞介导。我们发现L. reuteri治疗减少了EAE小鼠中的T(H)1/T(H)17细胞及其相关细胞因子IFN-γ/IL-17。我们还发现,由EAE引起的肠道微生物群多样性的损失在很大程度上被L。reuteri治疗。基于分类学的肠道微生物群分析表明,三个“有益”的属双歧杆菌,普雷沃氏菌属和乳杆菌属与EAE的临床严重程度呈负相关,而属Anaeroplasma,Rikenellaceae和梭菌属与疾病的严重程度呈正相关。值得注意的是,L. reuteri处理协调地改变了这些EAE相关分类群的相对丰度。综上所述,益生菌L. reuteri改变了肠道微生物群,以调节EAE的免疫反应,使其成为未来研究中改变MS严重程度的新候选药物。
The gut microbiome plays an important role in immune function and has been implicated in multiple sclerosis (MS). However, how and if the modulation of microbiota can prevent or treat MS remain largely unknown. In this study, we showed that probiotic Lactobacillus reuteri DSM 17938 (L. reuten) ameliorated the development of murine experimental autoimmune encephalomyelitis (EAE), a widely used animal model of MS, a model which is primarily mediated by T(H)17 and T(H)1 cells. We discovered that L. reuteri treatment reduced T(H)1/T(H)17 cells and their associated cytokines IFN- gamma/IL-17 in EAE mice. We also showed that the loss of diversity of gut microbiota induced by EAE was largely restored by L. reuteri treatment. Taxonomy-based analysis of gut microbiota showed that three "beneficial" genera Bifidobacterium, Prevotella, and Lactobacillus were negatively correlated with EAE clinical severity, whereas the genera Anaeroplasma, Rikenellaceae, and Clostridium were positively correlated with disease severity. Notably, L. reuteri treatment coordinately altered the relative abundance of these EAE-associated taxa. In conclusion, probiotic L. reuteri changed gut microbiota to modulate immune responses in EAE, making it a novel candidate in future studies to modify the severity of MS.