The oral microbiome as a window into the pathobiology of multiple sclerosis, leading to new ideas for personalized microbial therapies

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Abstract Multiple Sclerosis (MS) affects roughly 2.3 million people worldwide, with Relapsing-Remitting Multiple Sclerosis (RRMS) making up 85% of all MS cases. Although the precise pathobiology of RRMS is not well understood, it is linked to both genetic and environmental factors with an emerging important environmental factor being the microbiome. Recent evidence has shown that the gut microbiota of MS patients differs from that of healthy individuals, suggesting it likely plays a role in pathobiology. However, the importance of the oral microbiome, which is the second most diverse microbiome (first being the gut), as a potential environmental factor is poorly understood. Prior research on the oral microbiome has shown that it can affect not only our oral health, but our systemic health. In fact, other neurodegenerative and autoimmune diseases have been linked with the oral microbiome dysbiosis including Alzheimer’s, Atherosclerosis, and rheumatoid arthritis. Thus, the investigation of the oral microbiome as an environmental factor in the pathobiology of MS is warranted and this proposal will address this gap in knowledge. To test this hypothesis, we will analyze oral biospecimens from 50 patients with RRMS and 50 healthy controls (HC). This cross-sectional comparison will look at the differences and similarities in microbial composition and its associated function between the two groups. Additionally, as the metabolome impacts host health and the microbiome can influence the host metabolome, we will utilize an untargeted metabolomics approach to determine whether MS and HC oral metabolites differ. Lastly, we will correlate the microbes and metabolites to identify the relationships between the oral microbiome and the host metabolites as well as utilize machine learning to identify the most significant features associated with the pathobiology of MS. Overall, this study will help in identifying specific oral microbes, microbial functional pathways, and host metabolite pathways that may be used as potential diagnostic biomarkers as well as therapeutic agents for patients with RRMS.