Skip to main content
Premium Trial:

Request an Annual Quote

Gut Microbiome in Multiple Sclerosis Varies by Disease Course, Treatment Approach

NEW YORK — The makeup of the gut microbiomes of people with multiple sclerosis varies based on their disease course and treatment, according to new findings from the International Multiple Sclerosis Microbiome Study (iMSMS).

While the origins of MS remain unclear, both genetic and environmental factors are thought to influence the development of the autoimmune disorder. As gut microbiota have been tied to inflammatory conditions and as microbial changes have been noted in one form of MS, the international research team sought to study the gut microbiomes of more than 500 MS patients and 500 genetically unrelated healthy controls from the same household. As they reported in the journal Cell on Thursday, the researchers conducted shotgun metagenomic sequencing to find certain gut microbes were increased while others were decreased in number among individuals with MS, depending on their disease and treatment type.

"These results strongly support specific gut microbiome associations with MS risk, course and progression, and functional changes in response to treatment," Sergio Baranzini from the University of California, San Francisco, and iMSMS colleagues wrote in their paper.

The consortium recruited 576 individuals with MS and the same number of healthy household controls from seven different centers in the US, South America, and Europe to provide stool samples and survey responses. Following 16S rRNA analysis, the researchers found no differences in alpha diversity, a measure of within-sample diversity, between individuals with MS and controls. But they did note differences in beta diversity, a measure of between-sample diversity, by disease status.

More than a dozen microbial species were increased and half a dozen were decreased among individuals with untreated MS, compared to controls. Other microbial species, including Bacteroides and Prevotella members, varied in prevalence by MS type — relapsing-remitting or progressive MS — and severity.

Few differences were found between the functional potential of microbes but there were differences at the individual pathway level. For instance, the phytate degradation I pathway was enriched among MS patients, while pyruvate-producing carbohydrate metabolism pathways were reduced.

A number of species, including Akkermansia muciniphila, degrade phytate through the phytate degradation I pathway. The researchers noted that peptides from A. muciniphila, a mucin-degrading bacterium with pro-inflammatory effects, have been found to stimulate human myelin autoreactive CD4+ T cell clones, suggesting a possible role for molecular mimicry in MS pathogenesis.

Another mucus-degrading bacterium, Ruminococcus torques, was also enriched among individuals with MS.

What treatment approach individuals with MS underwent further affected their gut microbiomes. Individuals treated with oral therapies like fingolimod or dimethyl fumarate had reduced Bacteroides, Blautia, and Clostridium species, and those treated with injectable therapies like glatiramer acetate or interferon had decreased levels of Faecalibacterium prausnitzii, Dialister invisus CAG:218, and R. intestinalis.

Additionally, oral treatment with fingolimod led to metabolic changes, including reduced depletion of pyruvate-producing microbial pathways.

The researchers additionally examined the effect of diet on gut microbiome composition in MS to find that while individuals with MS tended to have healthier diets than household controls, diet only had a modest effect on MS-linked microbial taxa.

"The findings strongly support the presence of specific gut microbiome associations both with MS disease course and progression and [with] functional changes in response to treatment. The origin and biological relevance of these associations remain to be elucidated," Baranzini and colleagues added. "Nevertheless, our study supports the possibility that microbial manipulation and dietary intervention could be used as preventive and therapeutic strategies in MS."