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

Zhiwei Lu,Lei Si,Zhanhang Wang,Yingying Liu,Lili Ma,Xueying Ma,Xiuhua Wu,Zuying Kuang,Xuefei Li,Yuefeng Zhang,Man Zhang,Xiaohong Chen,Liping Shen,Xiuli Lin,Hao Chen,Xiaomeng Ma,Dengna Lin,Zhaoyu Chen

doi:10.1038/s41420-020-00309-8

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.

Highlights

Encephalitis, a neurological disorder caused by inflammation of the brain parenchyma, has an estimated incidence of 5–10 people per 100,000 people per year, this incidence is likely an underestimation[1]
Clinical characteristics of study participants We studied the fecal microbiomes in a large and wellcharacterized cohort comprising 54 newly diagnosed subjects with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis as well as 54 age, gender- and body mass index (BMI)-matched healthy controls (HCs)
BMI body mass index, PCS psychiatric symptoms, BPRS brief psychiatric rating scale. aMann–Whitney U test was used for continuous variables; values are expressed as the mean ± standard deviation if the data were normally distributed or as median and quartiles if the data were not normally distributed

Summary

Introduction

Encephalitis, a neurological disorder caused by inflammation of the brain parenchyma, has an estimated incidence of 5–10 people per 100,000 people per year, this incidence is likely an underestimation[1]. Discovered that AQP4 p63–76 contains strong homology to aa 204–217 of an adenosine triphosphate-binding cassette (ABC) transporter permease of a gut microbe— Clostridium perfringens. The gut microbiota has been reported to be associated with anxiety[6], memory[7], cognition[8], and hyperactivity[9]. These findings highlight the novel possibility that disturbances of the gut microbiota or MGB axis may contribute to the onset of CNS autoimmunity and neuropsychiatric manifestations

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