Effect of dimethyl fumarate on gut microbiota in patients with relapsing remitting multiple sclerosis: a prospective longitudinal pilot study
ECTRIMS Online Library. Ferri C. 09/13/19; 278432; P1229
Caterina Ferri
Caterina Ferri
Contributions
Abstract

Abstract: P1229

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Microbiology and virology

C. Ferri1, E. Baldin1, M. Castellazzi1, L.M. Caniatti2, E. Baldi2, M. Pugliatti1

1Department of Biomedical and Specialty Surgical Sciences, Interdepartmental Research Center for Neuroinflammation and Neurodegeneration, University of Ferrara, 2Multiple Sclerosis Center, Department of Neuroscience and Rehabilitation, S. Anna Hospital, Ferrara, Italy

Introduction: Several pre-clinical studies have shown that the gut microbiota is able to influence the development and course of experimental autoimmune encephalomyelitis. Multiple sclerosis (MS) appears to be associated with intestinal dysbiosis, which may trigger neuroinflammation. Immunomodulatory properties of the gut microbiota have made it a potential target for disease-modifying treatments (DMTs); emerging evidence suggests that DMTs for MS, such as dimethyl fumarate (DMF), could normalize the composition of the gut microbiota, although prospective longitudinal studies are still lacking.
Objective: We aimed to evaluate the potential effects of DMF on the gut microbiota in patients with relapsing remitting MS (RRMS).
Methods: We conducted a prospective longitudinal pilot study. Ten consecutive patients with diagnosis of RRMS and candidates to start DMF were recruited. Antibiotic use in the previous three months was an exclusion criterion. Stool specimens were collected before starting DMF and at predetermined time intervals (one week, one month, three and six months) after therapy initiation. The microbiota analysis included the evaluation of alpha diversity and taxonomic analysis at the phylum, family and genus level. A bifidobacterial profiling was also performed.
Results: Comparing before and after starting the treatment, the microbiota analysis showed a non-statistically significant modification of alpha diversity. DMF treatment was associated with mild decrease of the relative abundance of the phyla Firmicutes, Verrucomicrobia and Proteobacteria, while Bacteroidetes tended to increase. At genus level a slight reduction in the relative abundance of Lachnospira, Eubacterium coprostanoligenes and Akkermansia during DMF assumption was detected while Ruminococcaceae UCG002 was slightly increased.
Conclusions: In our population DMF did not significantly change the overall gut microbiota composition and alpha diversity, but some changes were observed at phylum and genus level, with special regard to some genera belonging to Clostridiales order. We therefore hypothesize that the effect of DMF on the gut microbiota composition may partially explain the immunomodulatory effect of this drug. Further investigations are needed to confirm this hypothesis.
Disclosure: Ferri C has received travel grants from Sanofi Genzyme, Merck Serono, Biogen and Novartis.
Baldin E has received travel grants from Sanofi Genzyme and Biogen.
Castellazzi M: nothing to disclose.
Caniatti LM has received fees as speaker or travel grants from Roche, Teva, Merck Serono, Sanofi Genzyme and Biogen.
Baldi E has received fees as speaker or travel grants from Roche, Teva, Merck Serono, Sanofi Genzyme and Biogen.
Pugliatti M has carried out consulting activity for Bayer Schering, Sanofi Genzyme, Biogen and Merck Serono. She has received fees as speaker or travel grants from Bayer Schering, Biogen Idec, Sanofi Genzyme and Merck Serono.

Abstract: P1229

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Microbiology and virology

C. Ferri1, E. Baldin1, M. Castellazzi1, L.M. Caniatti2, E. Baldi2, M. Pugliatti1

1Department of Biomedical and Specialty Surgical Sciences, Interdepartmental Research Center for Neuroinflammation and Neurodegeneration, University of Ferrara, 2Multiple Sclerosis Center, Department of Neuroscience and Rehabilitation, S. Anna Hospital, Ferrara, Italy

Introduction: Several pre-clinical studies have shown that the gut microbiota is able to influence the development and course of experimental autoimmune encephalomyelitis. Multiple sclerosis (MS) appears to be associated with intestinal dysbiosis, which may trigger neuroinflammation. Immunomodulatory properties of the gut microbiota have made it a potential target for disease-modifying treatments (DMTs); emerging evidence suggests that DMTs for MS, such as dimethyl fumarate (DMF), could normalize the composition of the gut microbiota, although prospective longitudinal studies are still lacking.
Objective: We aimed to evaluate the potential effects of DMF on the gut microbiota in patients with relapsing remitting MS (RRMS).
Methods: We conducted a prospective longitudinal pilot study. Ten consecutive patients with diagnosis of RRMS and candidates to start DMF were recruited. Antibiotic use in the previous three months was an exclusion criterion. Stool specimens were collected before starting DMF and at predetermined time intervals (one week, one month, three and six months) after therapy initiation. The microbiota analysis included the evaluation of alpha diversity and taxonomic analysis at the phylum, family and genus level. A bifidobacterial profiling was also performed.
Results: Comparing before and after starting the treatment, the microbiota analysis showed a non-statistically significant modification of alpha diversity. DMF treatment was associated with mild decrease of the relative abundance of the phyla Firmicutes, Verrucomicrobia and Proteobacteria, while Bacteroidetes tended to increase. At genus level a slight reduction in the relative abundance of Lachnospira, Eubacterium coprostanoligenes and Akkermansia during DMF assumption was detected while Ruminococcaceae UCG002 was slightly increased.
Conclusions: In our population DMF did not significantly change the overall gut microbiota composition and alpha diversity, but some changes were observed at phylum and genus level, with special regard to some genera belonging to Clostridiales order. We therefore hypothesize that the effect of DMF on the gut microbiota composition may partially explain the immunomodulatory effect of this drug. Further investigations are needed to confirm this hypothesis.
Disclosure: Ferri C has received travel grants from Sanofi Genzyme, Merck Serono, Biogen and Novartis.
Baldin E has received travel grants from Sanofi Genzyme and Biogen.
Castellazzi M: nothing to disclose.
Caniatti LM has received fees as speaker or travel grants from Roche, Teva, Merck Serono, Sanofi Genzyme and Biogen.
Baldi E has received fees as speaker or travel grants from Roche, Teva, Merck Serono, Sanofi Genzyme and Biogen.
Pugliatti M has carried out consulting activity for Bayer Schering, Sanofi Genzyme, Biogen and Merck Serono. She has received fees as speaker or travel grants from Bayer Schering, Biogen Idec, Sanofi Genzyme and Merck Serono.

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