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

Abstract

Introduction: Patients with multiple sclerosis may have a distinct gut microbiota profile. Delayedrelease 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 sideeffects. Methods: Thirty-six patients with relapsing-remitting multiple sclerosis received either dimethyl fumarate (n ¼ 27) or an injectable multiple sclerosis disease-modifying therapy (glatiramer acetate or interferons, n ¼ 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 ¼ 21) we observed a trend of reduced Actinobacteria (p ¼ 0.03, Q FDR ¼ 0.24) at two weeks, mainly driven by Bifidobacterium (p ¼ 0.06, Q FDR ¼ 0.69). At 12 weeks, we observed an increased abundance of Firmicutes (p ¼ 0.02, Q FDR ¼ 0.09), mostly driven by Faecalibacterium (p ¼ 0.01, Q FDR ¼ 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.

Dimethyl Fumarate Alleviates Dextran Sulfate Sodium-Induced Colitis, through the Activation of Nrf2-Mediated Antioxidant and Anti-inflammatory Pathways

“…Moreover, there is growing evidence that sulphate-reducing bacteria, an anaerobic microorganism that belongs to normal microbiota in the gastrointestinal tract, can be a trigger of intestinal inflammation and contribute to UC [27][28][29]. Interestingly, some recent studies have shown that treatment of DMF in the patients with MS also has an impact on altering microbiota composition [30,31]. In our current study, we didn't examine the gut microbiome change.…”

The Core of Gut Life: Firmicutes Profile in Patients with Relapsing-Remitting Multiple Sclerosis

“…Our result that disease-modifying therapy as an individual factor had not significantly contributed to the data variance was unexpected, as previous studies revealed DMT-related differences in the gut microbiota of MS patients: the dimethyl fumarate or interferon β-b treatment decreased the Firmicutes phylum relative abundance [ 60 , 61 ]. Yet, other studies reported an increased Firmicutes abundance, mostly driven by Fecalibacterium , in the dimethyl fumarate-treated patients [ 62 ], or no difference in the Firmicutes abundance between no-DMT and DMT cohorts [ 61 ]. However, in our study the observed 2% decrease in the Fecalibacterium abundance was not statistically significant and could hardly be physiologically relevant with its negligible contribution to the data variance.…”

Alterations of Gut Microbiota and the Brain-Immune-Intestine Axis in Patients With Relapsing-Remitting Multiple Sclerosis After Treatment With Oral Cladribine: Protocol for a Prospective Observational Study

“…The time point of 3 months after the start of treatment was chosen in order to be able to predict early in the treatment regimen whether a treatment response can be expected. Only one previous study investigated changes in microbiota after IMT and found a trend toward changes in microbiota after 2 and 12 weeks [ 15 ]. However, possibly due to a small sample size, after correction for multiple comparisons, none of their results seem to be significant.…”