Immunotherapy-mediated modulation of the gut microbiota in multiple sclerosis and associations with diet and clinical response-the effect of dimethyl fumarate therapy.

Background: Accumulating evidence supports a role of the microbiota in health and disease, including in multiple sclerosis (MS). How MS drugs affect the microbiota and whether this is part of their mode of action is yet unknown. Objectives: To assess how dimethyl fumarate (DMF) affects the gut microbiota and whether the microbiota is associated with clinical response or adverse events (AEs) to DMF or diet. Design: An observational cohort study, in which the microbiota from 45 patients with relapsing-remitting MS pre-DMF initiation and following 6 months of DMF therapy, and from 47 matched healthy controls, were compared, and associations with clinical and dietary data assessed. Data sources and methods: Microbial DNA was sequenced and analyzed using MicrobiomeAnalyst. The clinical response was assessed after 1-year DMF therapy based upon evidence of disease activity (relapse, ΔEDSS increase >1, or MRI activity compared to pre-treatment). Dietary data were obtained by food questionnaires. Results: Alterations in relative abundance of several microbes were identified post 6-month DMF therapy compared to pre-treatment, including an increase in Firmicutes, Conclusion: DMF immunotherapy is associated with modifications of the microbiota. The microbiota may affect the severity of AEs and the clinical response to DMF, and is potentially modulated by diet. Microbiota-based, personalized treatment approach, integrating pharmacotherapy with dietary components, carries potential to improved clinical outcome.