Multiple Sclerosis Discovery Could End Disease’s Chronic Inflammation

Andrea Merchak, a doctoral candidate in neuroscience, led the research for Alban Gaultier of the School of Medicine’s Department of Neuroscience and its Center for Brain Immunology and Glia, or BIG.

Scientists have struggled to understand the causes of MS, but recent research suggests an important role for the gut microbiome. UVA’s new findings bolster that, determining that an immune system controller found in “barrier tissues” such as the intestine plays a vital role in the disease. This regulator can reprogram the gut microbiome to promote harmful, chronic inflammation, the researchers found.

Gaultier and his collaborators blocked the activity of the regulator, called “aryl hydrocarbon receptor” in immune cells called T cells, which led to a dramatic effect on the production of bile acids and other metabolites in the microbiomes of lab mice. With this receptor out of commission, inflammation decreased and the mice recovered.

The findings suggest that doctors may one day be able to take a similar approach to interrupt the harmful inflammation in people with MS. That will take much more research, however. Scientists will need a better understanding of the interactions between the immune system and the microbiome, the UVA researchers say.

Still, UVA’s new research lays an important foundation for future efforts at targeting the microbiome to reduce inflammation responsible for multiple sclerosis and other autoimmune diseases.

“Due to the complexity of the gut flora, probiotics are difficult to use clinically. This receptor can easily be targeted with medications, so we may have found a more reliable route to promote a healthy gut microbiome,” Merchak said. “Ultimately, fine-tuning the immune response using the microbiome could save patients from dealing with the harsh side effects of immunosuppressant drugs.”

Gaultier and his team are part of UVA’s TransUniversity Microbiome Initiative, which serves as the central hub for the University’s cutting-edge microbiome research. The initiative aims to expand understanding of the microbiome to better treat and prevent disease.

Gaultier and his collaborators have published their findings in the scientific journal PLOS Biology. The research team consisted of Merchak, Hannah J. Cahill, Lucille C. Brown, Ryan M. Brown, Courtney Rivet-Noor, Rebecca M. Beiter, Erica R. Slogar, Deniz G. Olgun and Gaultier. The researchers had no financial interest in the work.

The research was supported by the National Institutes of Health, grants R33 MH108156, T32 NS115657 and T32 GM008136; the UVA Wagner fellowship; the Owens Family Foundation; the UVA TransUniversity Microbiome Initiative; and the UVA Presidential Fellowship in Neuroscience.

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