Study Associates Gut Bacteria with MS Risk and Disease Stage

Researchers have been increasingly examining the human gut microbiota's role in numerous diseases and disorders, including multiple sclerosis (MS). Within recent MS literature, researchers obtained inconsistent results with human subjects, partly due to small sample sizes and environmental effects on an individual's gut bacteria. However, a team of researchers addressed these challenges by participating in the International Multiple Sclerosis Microbiome Study (iMSMS), which recruited and analyzed the microbiomes of numerous MS patients from around the globe.

The findings, published in the journal Cell, examined the gut microbiomes of 576 MS patients in the United States, UK, Spain, and Argentina. The team selected genetically unrelated participants from the same households as the patients for their controls. This was the first time this innovative approach was used for human MS research.

Due to this methodology, lead author Sergio Baranzini, Ph.D., and colleagues identified dozens of new bacterial species associated with MS and confirmed other species that had previously only been associated with the disease. Additionally, they found that the most significant source of variation in bacteria species originated from the participants' geographical location, which confirmed the importance of considering local, healthy variations in gut microflora in research samples. The second most significant source of variation was identified to be the participant's disease status.

"We were surprised by the number of species that were differentially present in MS when compared to controls," says Baranzini. "When looking at the microbiome, there are two questions that usually are asked," he said. "The first one is 'Who's there?' This is what we're trying to answer in this paper. The second is, 'What are they doing?'" 

While the team still has more work ahead of them to address that second question, Baranzini still feels like this work will have far-reaching implications. "Knowing which genes from which species we are able to identify in cases and controls, we can now start to reconstruct which potential pathways are active in patients and controls," Baranzini states. 

The team also found that patients treated with interferon beta-1a, an old immunomodulating therapy for MS, had lower concentrations of short fatty-acid chains in their feces and higher concentrations within their blood. Short-chain fatty acids are essential for healthy cell structure and fight against inflammation, suggesting that the interferon's mechanism of action increases the transportation of these molecules from the gut to the bloodstream.

The iMSMS team will continue this work with new patients in Germany and Canada to increase their sample cohort to 2,000 participants. Additionally, they plan to follow a subset of the participants over two years to analyze how their gut microflora changes in response to treatment, lifestyle changes, and disease progression.

"This is an example of how big science can only be achieved collaboratively," says Baranzini. "In the iMSMS, we really brought together the best and the brightest researchers in the microbiome research field and in multiple sclerosis, and they're all pulling towards the same objective."