Although multiple sclerosis (MS) is on the more rare side, it greatly disrupts the lives of people who have it and all close to them, and all without a cause. Now, UC San Francisco is behind an international research consortium demonstrating significant differences between the gut bacterial environment between people with MS and people without, and also between MS patients receiving different therapies. Additionally, the team discovered new paths that some of the bacteria take to promote disease progression.
Previous research has shown an association between the gut and multiple sclerosis in mice. There have been few human studies, and even less that have produced strong findings due to poor study design that doesn’t account for geography. A 2015 study points out that including environmental and household dynamics in research can strengthen study design, and thus results.
To avoid making the same mistakes, the scientists participating in the International Multiple Sclerosis Microbiome Study (IMSMS) recruited 576 MS patients from the U.S., United Kingdom, Spain, and Argentina. For their controls, they chose the same amount of genetically unrelated participants from the same households as the patients.
Researchers say it’s the first study of its size to use such groundbreaking methodology. “This is the reference study that will be used by the field for years to come,” notes lead author Sergio Baranzini, PhD, a member of the UCSF Weill Institute for Neurosciences.
The team identified dozens of new gut bacterial species linked to multiple sclerosis and confirmed other bacteria that had previously shown a relationship. Further, they report that geography was the biggest factor contributing to variations in species type. This goes to show how crucial it was for Baranzini and colleagues to account for environmental factors and the effect on the gut. The second factor was disease status, which is what they hypothesized.
Some of the identified MS-associated bacteria appears to play a role in helping humans digest plant fiber from fruits and vegetables, which seems to be a problem in multiple sclerosis patients. Other bacteria seem to influence inflammation and cell energy.
As far as treatments, the team finds that patients treated with interferon beta-1a — the oldest therapy for MS — have lower concentrations of short-chain fatty acids (SCFa’s) in fecal samples, yet higher in their blood. SCFA’s have anti-inflammatory effects, suggesting that the medicine works by reducing it in the body. The team believes that their study and what’s known about this drug can help drive future therapies.
The IMSMS consortium hopes to expand their work to include up to 2000 participants total, including people Germany and Canada. This upcoming fall, the team will begin following some patients over a two-year period to monitor the evolution of their gut environment in response to therapy, diet, 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.”
This study is published in the journal Cell.