Functional changes in the gut microbiome of Multiple Sclerosis patients come along with an increased Vancomycin-resistant gene profile

The gut microbiome influences immune function, and its dysregulation has been linked to autoimmune diseases such as multiple sclerosis (MS). To reduce confounders of earlier single-center studies and 16S-based analyses, we performed a two-center metagenomic study including 61 treatment-naïve and 65 ocrelizumab-treated MS patients, compared with matched healthy controls. Treatment-naïve patients showed reduced microbial diversity and consistent taxonomic shifts across cohorts, including enrichment of Alistipes finegoldii and Bacteroides vulgatus and depletion of several Actinomycetota species. Functional profiling indicated altered carbohydrate metabolism and increased biosynthesis of L-citrulline and urea cycle intermediates, largely driven by A. finegoldii. Notably, vancomycin-resistance genes were significantly enriched, mainly contributed by Bacteroides and Streptococcus. Ocrelizumab-treated patients exhibited less pronounced microbial and functional alterations. These findings suggest that treatment-naïve MS is associated with a distinct dysbiotic and antibiotic-resistance-linked gut microbiome, potentially contributing to immune dysregulation.