Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice
Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice
复制标题
DOI：
10.1038/s41420-020-00309-8
复制
发表时间：
2020-08-11
影响因子：
7
通讯作者：
Chen, Xiaohong
中科院分区：
文献类型：
--
作者：
Chen, Hao;Chen, Zhaoyu;Chen, Xiaohong
微生物群-肠-脑轴的重要性已越来越被认为是自身免疫的主要调节剂。在这里，我们的目的是表征一个大的队列的治疗初治抗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。相对于HC，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。插补KEGG分析揭示了抗NMDAR脑炎肠道微生物组中功能模块的扰动。与HC相比，接受来自抗NMDAR脑炎患者的粪便微生物群移植（FMT）的微生物群耗尽的小鼠具有超敏反应和认知障碍。此外，抗NMDAR脑炎FMT小鼠显示脾脏和小肠固有层中的T细胞改变，Th 17细胞增加。总的来说，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，Th 17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。
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-naive 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.