Abstract
The gut microbiome has been increasingly recognized as an important factor in the pathogenesis of multiple sclerosis (MS). While MS medications and probiotic supplementation have been shown to independently modify gut microbial communities, their potential interaction remains unclear. In this study, we analyzed 16S rRNA gene sequencing data from the International Multiple Sclerosis Microbiome Study (iMSMS) to investigate whether probiotic use interacts with oral and non-oral medication routes to influence the gut microbiome in individuals with MS. Alpha and beta diversity analyses revealed no significant differences in microbial richness, evenness, or overall community composition across treatment groups. Similarly, no shifts toward microbiome profiles resembling those of untreated individuals with MS or healthy controls were observed, and predictive functional profiling showed no significant differences in pathway abundance. However, indicator species analysis found more indicator taxa present in probiotic-supplemented oral treatment groups compared to no probiotics and non-oral groups as well as identified three enriched taxa, Staphylococcus, Pediococcus, and Bacillus, potentially associated with probiotic use in oral treatment groups. Our findings suggest probiotic use does not significantly alter global gut microbiome composition but may be associated with subtle, taxa-specific changes in individuals receiving oral medications. Further investigation is needed to examine the possible functional and clinical implications of these localized microbial changes.