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

C Storm-Larsen; K-M Myhr; E Farbu; R Midgard; K Nyquist; L Broch; P Berg-Hansen; A Buness; K Holm; T Ueland; L-E Fallang; E Burum-Auensen; J R Hov; T Holmøy

doi:10.1177/2055217319888767

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

Mult Scler J Exp Transl Clin. 2019 Nov 15;5(4):2055217319888767. doi: 10.1177/2055217319888767. eCollection 2019 Oct-Dec.

Authors

C Storm-Larsen¹, K-M Myhr², E Farbu², R Midgard³, K Nyquist⁴, L Broch⁵, P Berg-Hansen¹, A Buness⁶, K Holm¹, T Ueland¹, L-E Fallang⁷, E Burum-Auensen⁸, J R Hov¹, T Holmøy¹

Affiliations

¹ Institute of Clinical Medicine, University of Oslo, Norway.
² Department of Clinical Medicine, University of Bergen, Norway.
³ Department of Neurology, Molde Hospital, Norway.
⁴ Department of Neurology, Innlandet Hospital Trust, Norway.
⁵ Department of Neurology, Drammen Hospital, Norway.
⁶ Norwegian PSC Research Center, Oslo University Hospital, Norway.
⁷ Previous Biogen, Norway.
⁸ Biogen, Norway.

Abstract

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 butyrate-producing Faecalibacterium after 12 weeks treatment. The study was underpowered to link microbiota to gastrointestinal symptoms.

Keywords: Gastrointestinal microbiome; clinical trial; dimethyl fumarate; faecalibacterium; gastrointestinal symptoms; multiple sclerosis.