Multiple Sclerosis Is Associated With Changes in the Gut Microbiome

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson

Researchers have found a correlation between multiple sclerosis (MS) and changes in the human gut microbiome, according to data published June 28 in Nature Communications. "There are a number of ways that the microbiome could play a role in MS, and this opens up a whole new world of looking at the disease in a way that it's never been looked at before," said Howard L. Weiner, MD, Director of the Partners MS Center and Codirector of the Ann Romney Center for Neurologic Disease at Brigham and Women's Hospital in Boston.

Previous studies have suggested a connection between bacteria in the gut and MS, as well as inflammatory bowel disease, type 1 diabetes, and rheumatoid arthritis. In one study of 20 patients with MS and 40 healthy controls, researchers found decreased numbers of Faecalibacterium, Prevotella, and Anaerostipes in patients with MS. The connection between microbiota, treatment, and changes in immunity, however, was not investigated. Because the gut microbiome plays a vital role in immune function and autoimmune disease, Dr. Weiner and his colleagues conducted research to detect changes in the intestinal microbiota in patients with MS, compared with controls. "If further studies demonstrate that these candidate microorganisms play an active role in either contributing to or ameliorating MS, then there is potential to develop new diagnostics and therapies to combat the disease," said Dr. Weiner.

The investigators examined data and collected stool samples from 60 untreated and treated patients with relapsing-remitting MS and 43 healthy control subjects. Subjects were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis study. None of the patients had an active relapse at the time of study enrollment. For the study, microbial DNA was removed from fecal samples, and gene sequencing was performed with two platforms using primers targeting the V3-5 or the V4 variable regions. Investigators also collected breath samples from a second cohort of 41 patients with MS and 32 controls after they participated in an overnight fast.

Patients with MS had microbial changes in the gut that were associated with the activity of genes that play a role in the immune system. Specifically, researchers found that the gut microbiome in patients with MS contained higher levels of Methanobrevibacter and Akkermansia, and lower levels of Butyricimonas, compared with healthy controls. Increased levels of Methanobrevibacter in patients with MS resulted in higher levels of methane in their breath samples, said the researchers. In addition, patients with MS on disease-modifying treatment had increased abundances of Prevotella and Sutterella, and decreased levels of Sarcina, compared with untreated patients with MS.

"This work provides a window into how the gut can affect the immune system, which can then affect the brain. Characterizing the gut microbiome in those with MS may provide new opportunities to diagnose MS and point us toward new interventions to help prevent disease development in those who are risk," said Dr. Weiner.

The researchers plan to continue studying the connection between gut bacteria and the immune system in hopes of developing improved treatment strategies. "In addition, characterization of the gut microbiome in MS may provide biomarkers for assessing disease activity and could theoretically be an avenue to prevent MS in young at-risk populations," said Dr. Weiner.

—Erica Robinson