Gut microbiota composition during a 12-week intervention with delayed-release dimethyl fumarate in multiple sclerosis - a pilot trial

Introduction: Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayed-release dimethyl fumarate is an orally administered drug for relapsing-remitting multiple sclerosis, which has been associated with gastrointestinal side-effects in some patients. Objectives: The purpose of this study was to determine if dimethyl fumarate alters the abundance and diversity of commensal gut bacteria, and if these changes are associated with gastrointestinal side-effects. Methods: Thirty-six patients with relapsing-remitting multiple sclerosis received either dimethyl fumarate (n = 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n = 9) for 12 weeks. Stool samples were collected at baseline, two and 12 weeks. We included 165 healthy individuals as controls. Results: At baseline, 16 microbial genera were altered in multiple sclerosis patients compared with healthy controls. In the dimethyl fumarate-treated patients (n = 21) we observed a trend of reduced Actinobacteria (p = 0.03, Q(FDR) = 0.24) at two weeks, mainly driven by Bifidobacterium (p = 0.06, Q(FDR) = 0.69). At 12 weeks, we observed an increased abundance of Firmicutes (p = 0.02, Q(FDR) = 0.09), mostly driven by Faecalibacterium (p = 0.01, Q(FDR) = 0.48). Conclusions: This pilot study did not detect a major effect of dimethyl fumarate on the gut microbiota composition, but we observed a trend towards normalization of the low abundance of butyrateproducing Faecalibacterium after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.