Relapsing-Remitting Multiple Sclerosis Is Associated With a Dysbiotic Oral Microbiome.

Objective: Multiple sclerosis (MS) is a chronic autoimmune disorder characterized by inflammation, demyelination, and neurological impairment. While the gut microbiota's role in MS is extensively studied, the association between the oral microbiota and MS remains underexplored, particularly in North American cohorts. This study aimed to investigate the microbiota (bacterial) composition as well as functional pathways and immune profiles of the oral cavity in 60 patients with relapsing-remitting MS (RRMS), stratified by treatment status, compared to 44 healthy controls (HC).

Methods: Unstimulated saliva was collected for genomic DNA extraction and salivary cytokine quantification. Oral bacterial composition and diversity were analyzed using 16S rRNA sequencing, with functional pathways inferred using PICRUSt2. Salivary cytokine levels were measured via multiplex immunoassays. LEfSe and random forest models identified key discriminatory taxa, and correlations between microbiota and cytokines were assessed using Spearman's rank analysis.

Results: RRMS patients exhibited distinct microbial communities compared to HC and a higher Bacteroidota to Firmicutes ratio. Key taxa such as Campylobacter, Lachnoanaerobaculum, and Porphyromonas were enriched in RRMS. Functional profiling revealed 49 differentially abundant pathways, including the enrichment of lipopolysaccharide biosynthesis in MS. Elevated levels of IFN-γ, IL-6, and other cytokines correlated with the altered microbiome. IL-21, elevated in HC, correlated with anti-inflammatory pathways, suggesting a protective role in immune homeostasis.

Interpretation: This study provides, for the first time, insights into oral microbiome-host interactions in North American RRMS patients, underscoring the interplay between microbial dysbiosis, functional pathways, and immune dysregulation. The oral microbiome shows potential as a biomarker for MS-related immune alterations.