Alterations in Gut Microbiome-Host Relationships After Immune Perturbation in Patients With Multiple Sclerosis

作者：Vinod K. Gupta, Guneet Janda, Heather K. Pump, Nikhil Lele, Isabella Cruz, Inessa Cohen, William Ruff, David A. Hafler, Jaeyun Sung, Erin E. Longbrake · 发表于：Neurology Neuroimmunology & Neuroinflammation · 年份：2025 · DOI：10.1212/nxi.0000000000200355 · 被引用次数：18 · 研究领域：Gut microbiota and health、Multiple Sclerosis Research Studies、Vagus Nerve Stimulation Research

BACKGROUND AND OBJECTIVES: Gut microbial symbionts have been shown to influence the development of autoimmunity in multiple sclerosis (MS). Emerging research points to an important relationship between the microbial-IgA interface and MS pathophysiology. IgA-secreting B cells are observed in the MS brain, and shifts in gut bacteria-IgA binding have been described in some patients with MS. However, the relationships between the gut microbiome and the host immune response, particularly regarding B-cell-depleting immunomodulation, remain underexplored. This study aimed to evaluate the composition of the gut microbiome in patients with newly diagnosed MS at baseline and after B-cell depletion, using long-read sequencing for enhanced taxonomic resolution. We further aimed to investigate the host/microbiome interface by evaluating microbe/immunoglobulin A relationships. METHODS: We collected stool samples from 43 patients with newly diagnosed, untreated MS and 42 matched healthy controls. Nineteen patients with MS initiated anti-CD20 monoclonal antibody treatment and donated additional stool samples after 6 months of treatment. We evaluated the host-microbial interface using bacterial flow cytometry and long-read 16S rRNA gene amplicon sequencing. We used Immune Coating Scores to compare the proportions of bacteria identified in the IgA-coated vs IgA-uncoated bacterial fractions. RESULTS: ) whose IgA-coating became more aligned with controls after therapy. DISCUSSION: This analysis ...