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Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice.
Cell Death Discovery ( IF 6.1 ) Pub Date : 2020-08-11 , DOI: 10.1038/s41420-020-00309-8
Hao Chen 1 , Zhaoyu Chen 1 , Liping Shen 1 , Xiuhua Wu 2 , Xueying Ma 1 , Dengna Lin 3 , Man Zhang 4 , Xiaomeng Ma 1 , Yingying Liu 1 , Zhanhang Wang 5 , Yuefeng Zhang 6 , Zuying Kuang 5 , Zhiwei Lu 6 , Xuefei Li 7 , Lili Ma 1 , Xiuli Lin 1 , Lei Si 1 , Xiaohong Chen 1
Affiliation  

The significance of the microbiota-gut-brain axis has been increasingly recognized as a major modulator of autoimmunity. Here, we aim to characterize the gut microbiota of a large cohort of treatment-naïve anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis patients relative to that of healthy controls (HCs). Relative to HCs, anti-NMDAR encephalitis patients had a decreased microbiome alpha-diversity index, marked disturbances of gut microbial composition and intestinal permeability damage. Disturbed microbiota in anti-NMDAR encephalitis patients might be linked with different clinical characteristics. Imputed KEGG analysis revealed perturbations of functional modules in the gut microbiomes of anti-NMDAR encephalitis. Compared to HCs, microbiota-depleted mice receiving fecal microbiota transplantation (FMT) from anti-NMDAR encephalitis patients had hypersensitivity and cognitive impairment. Furthermore, anti-NMDAR encephalitis FMT mice showed altered T cells in the spleen and small intestine lamina propria with an increased Th17 cells. Overall, this study first suggests that the anti-NMDAR encephalitis microbiome itself can influence neurologic, Th17 response and behavioral function. The gut microbiota is a potential therapeutic target for anti-NMDAR encephalitis.



中文翻译:

自身免疫性脑炎患者的粪便微生物群移植可调节小鼠的 Th17 反应和相关行为。

人们越来越认识到微生物群-肠-脑轴作为自身免疫的主要调节剂的重要性。在这里,我们的目的是描述一大群未经治疗的抗N-甲基-d-天冬氨酸受体(抗 NMDAR)脑炎患者相对于健康对照(HC)的肠道微生物群特征。与HCs相比,抗NMDAR脑炎患者的微生物组α多样性指数降低,肠道微生物组成明显紊乱,肠道通透性受损。抗 NMDAR 脑炎患者的微生物群紊乱可能与不同的临床特征有关。估算 KEGG 分析揭示了抗 NMDAR 脑炎肠道微生物组功能模块的扰动。与 HC 相比,接受抗 NMDAR 脑炎患者粪便微生物移植 (FMT) 的微生物群耗尽小鼠出现过敏和认知障碍。此外,抗 NMDAR 脑炎 FMT 小鼠的脾脏和小肠固有层中的 T 细胞发生改变,Th17 细胞增加。总体而言,这项研究首先表明抗 NMDAR 脑炎微生物组本身可以影响神经系统、Th17 反应和行为功能。肠道微生物群是抗 NMDAR 脑炎的潜在治疗靶点。

更新日期:2020-08-11
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