The neuromyelitis optica spectrum disorder (NMOSD) is a rare neuroinflammatory disorder of the central nervous system that involves relapses and remissions (Wingerchuk and Lucchinetti, 2022). Recently, new biologics targeting the interleukin-6 pathway or B cells have shown better efficacy than traditional immunosuppressants in treating NMOSD (Levy et al., 2021). Although rituximab (RTX), a monoclonal antibody targeting CD20 on B lymphocytes, has proven effective in improving disability and reducing relapse rates in NMOSD, some patients still experience recurrence (Wang et al., 2021). This raises concerns about the underlying immunopathogenesis between RTX and NMOSD.

The gut microbiota emerges as a crucial environmental factor influencing disease relapse and progression, highlighting the significant role of epigenetic mechanisms in NMOSD pathogenesis (Cui et al., 2020). Numerous studies have suggested the association between dysbiosis of gut microbiota and NMOSD (Junli Gong et al., 2019). The gut microbiota significantly impacts various aspects of B cells, including activation, development, function and differentiation, potentially contributing to the pathogenesis of immune disorders. For instance, gut microbiota can influence B cells to form cytokines, either promoting inflammation or maintaining homeostasis (Campbell et al., 2021). Furthermore, the microbiota is essential for interactions between T follicular helper (Tfh) cells and B cells in the gut. Mice raised in a germ-free environment lack Tfh development, leading to a deficiency in IgA+ B cells in the gut. This suggests that changes in the gastrointestinal environment may affect the regulation of T and B cells. However, research on whether B cell depletion could shape gut microbiota in NMOSD is limited. To date, the comprehensive analysis of the impact of B cell depletion treatment, various cytokines, and their correlation with the gastrointestinal environment has not been thoroughly conducted.

To address this issue, we conducted a rigorous analysis of the gut microbiome and various cytokines in a large cohort of NMOSD patients. We collected samples both before and three months after RTX treatment, aiming to understand how RTX-related immune responses might influence changes in the gastrointestinal environment. Additionally, exploring alterations in metabolic pathways may provide insights into the molecular mechanisms of RTX-related B cell depletion treatment.