Abstract
Multiple sclerosis (MS) is an autoimmune disease that targets the myelin in the central nervous system, leading to severe neurodegeneration. Although there is no cure, disease-modifying therapies (DMTs) are used to slow disease progression and manage symptoms. In studies of MS and of the relapsing-remitting subtype (RRMS), DMTs have been shown to alter the gut microbiome. Previous research identifies the microbiome as a potential driving factor for MS disease progression, therefore, understanding the impacts of DMTs on this system is crucial for effective MS treatment. However, the impacts of DMTs on the primary progressive MS (PPMS) and secondary progressive MS (SPMS) subtypes remain underexplored. This study investigates the potential effects of DMTs on the gut microbiome of PPMS and SPMS patients, grouped as progressive MS (PMS) patients. DMTs were grouped by mechanism into two categories: immunomodulators and T/B cell therapies. Using stool samples from treated PMS patients, untreated PMS patients, and genetically unrelated healthy household controls, we performed microbial diversity, differential abundance, and potential functional pathway. Ultimately, our research found no significant differences in gut microbial diversity or indicator taxa between PMS treatment status and across treatment types. We discovered few commensal species unique to treatment groups and identified consistent depletion of anti-inflammatory taxa in samples from DMT-treated patients. Moreover, our research suggests that immunomodulators may alter metabolic, stress response, and drug resistance-related functional pathways. Overall, more research is necessary to elucidate the relationship between DMTs and the gut microbiome in PMS.