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To elucidate cross-sectional patterns and longitudinal changes of oral and stool microbiota in multiple sclerosis (MS) patients and the effect of B-cell depletion. We conducted an observational, longitudinal clinical cohort study analysing four timepoints over 12 months in 36 MS patients, of whom 22 initiated B-cell depleting therapy with ocrelizumab and a healthy control group. For microbiota analysis of the oral cavity and the gut, provided stool and oral swab samples underwent 16S rDNA sequencing and subsequent bioinformatic analyses. Oral microbiota-patterns exhibited a reduced alpha-diversity and unique differential microbiota changes compared to stool such as increased levels of Proteobacteria and decreased abundance of Actinobacteria. Following B-cell depletion, we observed increased alpha-diversity in the gut and the oral cavity as well as a long-term sustained reduction of pro-inflammatory Gram-negative bacteria (e.g.,  Escherichia/Shigella ). MS patients have altered stool and oral microbiota diversity patterns compared to healthy controls, which are most pronounced in patients with higher disease activity and disability. Therapeutic B-cell depletion is associated with persisting regression of these changes. Whether these microbial changes are unspecific side-effects of B-cell depletion or indirectly modulate MS disease activity and progression is currently unknown and necessitates further investigations.

B-cell-depletion reverses dysbiosis of the microbiome in multiple sclerosis patients