Abstract
Multiple Sclerosis (MS) is a chronic central nervous system disorder that results in neurological disability due to inflammation that damages the myelin sheath. While current immunotherapies can attenuate symptoms, the absence of a definitive cure emphasizes the need to identify biological factors that influence disease pathogenesis. Associations between vitamin D intake and expanded disability status scale (EDSS), a snapshot metric quantifying MS disease progression, are inconsistent across clinical trials, suggesting that vitamin D’s impact on the progression of MS is currently not well known. Using 16S rRNA data from 410 MS patients collected in a household-controlled microbiome study, we aim to clarify the association between vitamin D and MS by exploring if and how the gut microbiome may contribute to the relationship between oral vitamin D intake and EDSS scores among MS patients. To evaluate this, we characterized taxonomic shifts and predicted metabolic pathways in the gut microbiome and assessed their relationships with EDSS. Oral vitamin D supplementation was associated with reduced gut microbial diversity in MS patients. Differences in overall gut microbiome composition were observed between vitamin D-supplemented MS patients, but these differences were unlikely due to vitamin D supplementation alone. Oral vitamin D supplementation was associated with an enrichment of SCFA-producing bacteria and a decreased presence of bacteria associated with neurobehavioural deficits. The functional analysis of MS patients on oral vitamin D supplementation also predicted reduced functional potential in vitamin K2 biosynthesis and purine nucleotide salvage pathways. Despite taxonomic and functional shifts, only weak correlations were found between a few microbial and pathway markers with EDSS. Therefore, while vitamin D may be associated with microbial gut composition and metabolic functions of MS patients, these alterations are only weakly correlated with MS severity.