Fecal microbiota transplantation from patients with autoimmune encephalitis modulates Th17 response and relevant behaviors in mice

Abstract

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.