Multiple sclerosis is a devastating disease that leads to disability through progressive nerve damage, which causes worsening physical and cognitive issues over time. Now, researchers have found that the gut microbiota and its metabolites play a significant role in multiple sclerosis progression, with specific microbial species and metabolic changes linked to worsening symptoms.

The findings, published in Cell Reports Medicine, suggest that modifying the microbiota could influence multiple sclerosis progression and provide new therapeutic targets.

Previous studies have shown that the gut microbiota is altered in people with multiple sclerosis, with some microbes linked to disease worsening and others associated with protection. However, it’s unclear how the microbiota and its metabolites are linked to long-term changes in disease severity and the transition to progressive multiple sclerosis — a stage of the disease where disability worsens over time.

To measure microbial composition and metabolic changes associated with disease severity, Luke Schwerdtfeger at Brigham and Women’s Hospital in Boston analyzed blood and stool samples from people with multiple sclerosis.

Microbial imbalance

The study participants were part of the Comprehensive Longitudinal Investigation of Multiple Sclerosis at the Brigham and Women’s Hospital (CLIMB study), which tracks people with multiple sclerosis over time, collecting clinical data, MRI scans and biological samples.

Certain gut bacteria, such as Alistipes and Bacteroides, are linked to worsening disability, while others, such as Streptococcus thermophilus and Eubacterium hallii, are associated with stability or improvement, the researchers found. 

Multiple sclerosis treatments appeared to influence gut bacteria composition, increasing beneficial microbes while reducing harmful ones. Some microbes, including Ruminococcus and Lachnoclostridium, were linked to better cognitive scores, while others were associated with worsening cognitive abilities.

Metabolic byproducts

People who transitioned to progressive multiple sclerosis had specific changes in metabolites, especially in lipids and bile acids. Certain metabolites were linked to worsening disability, while others were associated with stability. 

The researchers found that metabolic pathways related to vitamin B6, fatty acids and drug metabolism were more active in people transitioning to progressive multiple sclerosis. The team also identified gut microbes, including Akkermansia and Lachnospiraceae, that produce metabolites linked to disease progression.

The findings suggest that changes in gut bacteria and their byproducts play a role in worsening symptoms, offering potential targets for future treatments. However, the authors say, larger and more detailed studies are needed to better understand how gut microbes influence multiple sclerosis.