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A mouse study looks into the therapeutic potential that targeting immune cells in the gut might have in multiple sclerosis. Image credit: Vera Lair/Stocksy.
  • Multiple sclerosis (MS) affects more than 2.8 million people around the world.
  • MS is a chronic inflammatory disease that damages the body’s central nervous system.
  • Researchers from the University of Virginia believe they have found a way to block the inflammation causing MS via a mouse model.

Multiple sclerosis (MS) is a disease affecting more than 2.8 million people around the globe.

MS is a chronic inflammatory disease resulting in damage to the body’s central nervous system, including the brain. This damage causes a host of symptoms including muscle weakness, blurred vision, tremors, and even paralysis.

Now, scientists from the University of Virginia believe they have found a way to block the chronic inflammation responsible for MS.

Researchers used a mouse model to halt a specific receptor in the gut microbiome, resulting in decreased inflammation and improved symptoms.

The study was recently published in the journal PLOS Biology.

Andrea Merchak, a neuroscience PhD candidate at the University of Virginia and one of the lead researchers of this study, told Medical News Today it is important to have a way to disrupt the chronic inflammation causing MS because patients with MS often go through cycles of inflammation.

“These flare-ups — called relapses — will worsen any existing symptoms and sometimes initiate new ones,” she explained. “By attempting to interrupt this cycle, patients who have been diagnosed with MS will hopefully be able to slow or even halt the disease progression.”

According to Dr. Mark Allegretta, vice president of research for the MS Society of Canada, not involved in this study, inflammation is a key component of MS pathology, both in relapsing and progressive forms of the disease.

“Many cellular and humoral mediators of inflammation have been implicated, particularly for relapsing-remitting MS regarding the role of adaptive immune responses,” he told us.

“Evidence suggests that the innate immune system may be responsible for driving a low-level or indolent form of inflammation in progressive MS. Understanding the mechanism of the chronic, smoldering inflammation characteristic of progressive forms of MS is recognized as an important step in developing new therapeutic strategies.”

– Dr. Mark Allegretta

Merchak said while genetics play a role in determining who will ultimately get MS, researchers also know that environmental factors are equally if not more important.

“Some of these environmental factors that have been linked to the development of MS are diet, smoking, and stress,” she pointed out.

“All of these factors also change the gut microbiome,” noted Merchak. “Because the gut microbiome is so responsive to all of these elements and is so intimately connected to our immune system, it is a prime target for research.”

During the study, Merchak and her team used a mouse model to block the activity of a regulator in immune cells within the gut microbiome called the aryl hydrocarbon receptor (AHR).

The AHR has previously been implicated in other inflammatory diseases, such as rheumatoid arthritis and asthma.

“We were able to disrupt the inflammation that causes MS in our mouse model twofold,” Merchak detailed. “We first reduced the activity of a receptor that lives in the immune cells in the lining of the intestine.”

“This interrupted the cycle of inflammation, but we also saw that it increased the amount of bile salts in the intestine. These are chemicals that are used to digest food in your stomach,” she explained.

“We decided to figure out if increasing the amount of bile salt was enough to have the same effects and it was,” Merchak continued. “Mice that we fed with one of the bile salts had interrupted inflammation as well.”

After reading this study, Dr. Allegretta said that, in addition to the effects on T cells described in this study, AHR activity can influence the mouse MS model through innate immune cell types including natural killer cells, macrophages, and dendritic cells, so more research is needed to fully understand the contribution to pathogenesis by the different cell types.

“Importantly, AHR agonist activity tested in the plasma of people with progressive MS has been shown to correlate with disease activity,” he added.

“This suggests the findings may be translatable, so additional research in people with MS and appropriate control populations is needed to provide confidence to pursue this experimental therapeutic approach.”

With this research concluded, Merchak said she and her team plan to try and figure out which bile salts are most effective in mouse models and figure out what makes them work. Then, they plan to take these results to the clinic with some of their collaborators.

“These results open up two new avenues for future research,” she told us. “New therapies could target the receptor in the gut lining or they could target bile salts. There still needs to be extensive testing in the clinic, but these are two new avenues for exploration and discovery.”

MNT also spoke with Dr. Barbara Giesser, a neurologist and MS specialist at Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA, about this study.

She said this is an exciting study because it builds on a body of work showing that gut microbiome-immune system-brain interactions play an important part in MS.

“These results suggest that it may be potentially possible to decrease inflammation in persons with MS through agents that work directly on the gut microbiome, such as dietary manipulations,” she explained.

“Inflammation is one of the primary ways in which the immune system causes damage to the nervous system in persons with MS,” Dr. Giesser continued.

“All of our current disease-modifying therapies act to reduce inflammation at different points in the complicated inflammation pathway. This study demonstrated a novel way to block the action of some inflammatory immune cells by acting on a molecule involved in a pathway between the immune system and the gut microbiome,” the neurologist noted.