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 ( = 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons,  = 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 ( = 21) we observed a trend of reduced Actinobacteria ( = 0.03, Q = 0.24) at two weeks, mainly driven by ( = 0.06, Q = 0.69). At 12 weeks, we observed an increased abundance of Firmicutes ( = 0.02, Q = 0.09), mostly driven by ( = 0.01, Q = 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 butyrate-producing after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.