The gut microbiome plays a crucial role in immune function and has been implicated in several autoimmune disorders. This study investigates the gut microbiome in 60 multiple sclerosis (MS) patients and 43 healthy controls using 16S rRNA sequencing. The results show that MS patients have increased abundances of Methanobrevibacter and Akkermansia, and decreased abundances of Butyricimonas, which correlate with changes in gene expression related to dendritic cell maturation, interferon signaling, and NF-κB signaling in immune cells. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina compared to untreated patients. MS patients in a second cohort show elevated breath methane, consistent with increased gut Methanobrevibacter. The gut microbiome is a rich source of antigenic diversity and influences immune responses locally and systemically. The gut microbiome has been implicated in various immunologic disorders, including MS, inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In experimental autoimmune encephalomyelitis (EAE), a murine model for MS, altering the gut microbiome modulates central nervous system autoimmunity. The study also found that certain microbiota changes are associated with immune responses in MS, including correlations between microbial abundance and gene expression in T cells and monocytes. The gut microbiome may play a role in or be a consequence of MS pathogenesis. The study highlights the importance of the gut microbiome in immune function and autoimmune disease, and suggests that future research could explore the potential of microbiome-targeted therapies for MS. The study has limitations, including the inability to determine causality and the possibility of confounding factors. Overall, the study provides initial insights into the potential role of the microbiome in MS and suggests that future research could explore the microbiome as a potential target for treatment.The gut microbiome plays a crucial role in immune function and has been implicated in several autoimmune disorders. This study investigates the gut microbiome in 60 multiple sclerosis (MS) patients and 43 healthy controls using 16S rRNA sequencing. The results show that MS patients have increased abundances of Methanobrevibacter and Akkermansia, and decreased abundances of Butyricimonas, which correlate with changes in gene expression related to dendritic cell maturation, interferon signaling, and NF-κB signaling in immune cells. Patients on disease-modifying treatment show increased abundances of Prevotella and Sutterella, and decreased Sarcina compared to untreated patients. MS patients in a second cohort show elevated breath methane, consistent with increased gut Methanobrevibacter. The gut microbiome is a rich source of antigenic diversity and influences immune responses locally and systemically. The gut microbiome has been implicated in various immunologic disorders, including MS, inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In experimental autoimmune encephalomyelitis (EAE), a murine model for MS, altering the gut microbiome modulates central nervous system autoimmunity. The study also found that certain microbiota changes are associated with immune responses in MS, including correlations between microbial abundance and gene expression in T cells and monocytes. The gut microbiome may play a role in or be a consequence of MS pathogenesis. The study highlights the importance of the gut microbiome in immune function and autoimmune disease, and suggests that future research could explore the potential of microbiome-targeted therapies for MS. The study has limitations, including the inability to determine causality and the possibility of confounding factors. Overall, the study provides initial insights into the potential role of the microbiome in MS and suggests that future research could explore the microbiome as a potential target for treatment.