Disease-modifying therapies alter gut microbial composition in MS.

Area of Science:

• Microbiome research
• Immunology
• Neurology

Background:

• Gut microbiota composition is increasingly recognized as a factor in immune system regulation.
• Alterations in gut bacteria have been implicated in the pathophysiology of various autoimmune diseases, including multiple sclerosis (MS).
• Disease-modifying therapies (DMTs) are standard treatments for MS, but their impact on the gut microbiome is not fully understood.

Purpose of the Study:

• To investigate the effects of glatiramer acetate (GA) and dimethyl fumarate (DMF) on the gut microbial composition in patients with relapsing MS.
• To identify specific bacterial taxa and functional pathways affected by these DMTs.

Main Methods:

• 16S rRNA gene sequencing was performed on fecal DNA from treatment-naive MS patients and those treated with GA or DMF.
• Operational Taxonomic Units (OTUs) were clustered using the GreenGenes database.
• Differential abundance and functional pathway analyses were conducted using established bioinformatics tools.

Main Results:

• Both GA and DMF treatments were associated with significant alterations in fecal microbiota composition compared to treatment-naive individuals.
• Specific bacterial families, Lachnospiraceae and Veillonellaceae, showed decreased abundance with both GA and DMF.
• Dimethyl fumarate (DMF) was further associated with decreased Firmicutes and Fusobacteria, and increased Bacteroidetes, while both therapies affected overlapping functional pathways.

Conclusions:

• Glatiramer acetate (GA) and dimethyl fumarate (DMF) administration significantly modifies the gut microbial landscape in MS patients.
• The observed changes in microbial composition and associated metabolic pathways may offer insights into MS pathophysiology.
• These findings suggest potential mechanisms underlying DMT efficacy and highlight the gut microbiome as a target for future therapeutic interventions in MS.