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.

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。