We enrolled untreated, new onset MS patients and healthy controls and obtained longitudinal samples of paired blood and stool. To date, 20 healthy controls, 46 baseline MS, 14 1-month, 15 6-month and 8 12-month post-ocrelizumab samples have been sequenced. Recruitment and follow up are ongoing; updated numbers will be presented. Gut microbiota were characterized using high-throughput long amplicon sequencing of the 16S-ITS-23S rRNA operon, allowing increased bacterial taxonomic resolution. We also performed IgA-Seq, differentiating immune-reactive (IgA-coated) bacteria from those not eliciting an immune response (IgA-uncoated).

Microbial alpha diversity was decreased in early MS compared to healthy controls; beta diversity also showed significant differences. Fecal alpha and beta diversity tended to normalize with increasing time on B-cell depletion. Analysis of composition of microbiomes (ANCOM) revealed that Bacteroides and Monoglobus genera were enriched in the overall and IgA-coated fraction of gut microbiota of MS patients, respectively. At baseline, MS was associated with decreased IgA-coated and increased IgM-coated gut bacteria. There were trends for normalization of this phenotype after B-cell depletion.

Untreated MS patients exhibit a dysregulated immune response to gut microbes. Moreover, MS patients had a less diverse and phenotypically distinct microbiome compared to healthy individuals. B-cell depletion was associated with trends for normalization of the gut microbiome.