Dysbiosis of intestinal microbiota in patients with neuromyelitis optica spectrum disorders

Objective: This study aimed to explore the specific microbial signatures and metabolomic profiles of fecal microbiota in patients with neuromyelitis optica spectrum disorders (NMOSD) and assess the effects of immunosuppressants on their gut microbiota using a longitudinal cohort study. Methods: We enrolled 21 treatment-naïve NMOSD patients and 21 matched healthy controls (HCs). Fecal microbial composition and metabolomic profiles were compared between groups using 16S rRNA gene sequencing and ultra-high-performance liquid chromatography-mass spectrometry. Subsequently, fecal samples from NMOSD patients were collected and reassessed after immunosuppressant treatment. Results: at the genus level (all with linear discriminant analysis scores > 4 and P < 0.001). Additionally, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States analysis identified 19 differentially abundant metabolites and 44 altered metabolic pathways in NMOSD patients compared to HCs. Immunosuppressive treatment for over six months may reduce these differences, shifting the gut microbiota composition and metabolite profiles of NMOSD patients closer to those of HCs. Interpretation: Our study revealed significant gut microbiome dysbiosis and metabolic abnormalities in patients with NMOSD, which were markedly alleviated after six months of immunosuppressive treatment. These preliminary findings suggest the gut microbiota biomarkers could serve as potential therapeutic targets in the future.