New Study Reveals Link between Gut Microbiota and Multiple Sclerosis

Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system that develops in genetically susceptible individuals and requires environmental triggers. A new study, published in the journal Science Translational Medicine, shows that gut microbiota could play a big role in the pathogenesis of this disease.

Under a high magnification of 12,960x, this SEM image revealed some of the morphologic details displayed by a number of joined, Gram-negative, rod-shaped Escherichia coli bacteria. Image credit: Janice Haney Carr, CDC.

In multiple sclerosis, the body’s own immune system attacks and damages the protective coating around nerve cells.

This coating is made up of myelin — a biological membrane of protein and fatty substances — which is why research efforts to find the disease’s target antigen have so far focused on the myelin membrane’s components.

The new findings suggest that it is worth broadening the research perspective to gain a better understanding of the pathological processes.

“T cells, i.e. the immune cells responsible for pathological processes, react to a protein called GDP-L-fucose synthase,” said lead author Dr. Mireia Sospedra of the University Hospital Zurich and colleagues.

“This enzyme is formed in human cells as well as in bacteria frequently found in the gastrointestinal flora of patients suffering from multiple sclerosis.”

“We believe that the immune cells are activated in the intestine and then migrate to the brain, where they cause an inflammatory cascade when they come across the human variant of their target antigen.”

The researchers plan to test the immunoactive components of GDP-L-fucose synthase using an approach that they have been pursuing for several years already.

“Our clinical approach specifically targets the pathological autoreactive immune cells,” Dr. Sospedra said.

“This approach differs radically from other treatments that are currently available, which throttle the whole immune system.”

“While these treatments often succeed in stopping the progression of the disease, they also weaken the immune system — and can thus cause severe side effects.”

“Our clinical approach involves drawing blood from multiple sclerosis patients in a clinical trial and then attaching the immunoactive protein fragments onto the surface of red blood cells in a laboratory.”

“When the blood is reintroduced into the bloodstream of patients, the fragments help re-educate their immune system and make it ‘tolerate’ its own brain tissue.”

“This therapeutic approach aims for effective targeted treatment without severe side effects.”

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Raquel Planas et al. 2018. GDP-l-fucose synthase is a CD4+ T cell–specific autoantigen in DRB3*02:02 patients with multiple sclerosis. Science Translational Medicine 10 (462): eaat4301; doi: 10.1126/scitranslmed.aat4301