Discussion
This analysis of gut microbial ASVs reveals shifts in taxonomic strains induced by immune modulation in MS.
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
Patients with untreated, newly diagnosed MS showed significant reductions in IgA-bound fecal microbiota compared with controls. Using multiple linear regression models adjusted for potential confounders, we observed significant (p < 0.05) changes in the abundance and prevalence of various strain-level gut bacteria amplicon sequence variants (ASVs) within both total and IgA-coated bacterial fractions. Some changes (e.g., decreased relative abundance of a Faecalibacterium prausnitzii variant in MS) were consistent with previous reports, while others (e.g., increased relative abundance and prevalence of Monoglobus pectinyliticus in MS) were novel. Immune Coating Scores identified subsets of organisms for which normal IgA-coating patterns were disrupted at the onset of MS, as well as those (particularly Akkermansia muciniphila) whose IgA-coating became more aligned with controls after therapy.