Ongoing research is finding possible links between microorganisms living in the gut and MS.
Multiple sclerosis (MS) is a progressive disease, which means it becomes worse over time.
With about 400,000 people in the United States, and about 2.5 million people around the world, living with the condition, the need to find ways to better treat and manage the disease has led scientists into a whole new realm of research: how the “gut microbiome” — the genetic material of all the critters living in our digestive tract — might open doors to new MS treatments in the future.
What Exactly Is Multiple Sclerosis?
MS is a chronic disease in which the body abnormally attacks parts of its own nervous system. It’s considered an immune-mediated disease because it involves immune system attacks. Most experts — though not all — consider it to be an autoimmune disease, meaning the immune system is reacting against a normally occurring protein as if it were a foreign protein. But the specific protein, or antigen, being attacked has not been identified in MS.
With MS, the immune system specifically attacks myelin, the fatty sheath covering and protecting nerve fibers in the brain and spinal cord, as well as the cells that produce myelin, called oligodendrocytes.
The damaged myelin forms scar tissue, called sclerosis, and allows the underlying nerve fibers to come under attack as well. Damaged nerves means interference in the signals traveling between the brain and spinal cord and the rest of the body, leading to the tell-tale symptoms of the disease: numbness, difficulty speaking, poor muscle coordination, blurred vision, and severe fatigue.
What Is the Gut Microbiome?
In addition to our own cells, our bodies contain trillions of microorganisms — bacteria, viruses, fungi, and archaeal cells — collectively called microbiota. Their combined DNA is called the microbiome. Some may be harmful, but most are beneficial.
“These bacteria help us digest our food, provide essential vitamins, and assist in the development of our immune and nervous systems,” says Sarkis Mazmanian, PhD, a professor of microbiology at the California Institute of Technology in Pasadena. “Many of them protect us from disease.”
The vast majority of those bacteria live in our digestive system, as do more than 70 percent of all the white blood cells in the body. Hence the gut, which includes the large and small intestines, is a major organ of both the digestive and immune systems. That’s because the bacterial composition of the human gut plays a role in healthy immune functioning in the body.
“The gut is the second largest site of exposure of the body to the outside world after the skin, which is a largely impermeable barrier,” explains Daniel Mielcarz, PhD, a professor of microbiology and immunology at Dartmouth’s Geisel School of Medicine in Hanover, New Hampshire, and coauthor of a study review on the gut microbiome published in Current Treatment Options in Neurology in April 2015.
“In most people, a delicate homeostasis develops, with the immune system ignoring commensal (normal) bacteria and food proteins, but actively eliminating pathogens,” Dr. Mielcarz says. “In some people, an imbalance develops, leading to inflammatory bowel diseases like Crohn’s disease and ulcerative colitis, and growing evidence from animal models and clinical studies in humans shows that these imbalances can play a role in systemic illness as well.”
A healthy gut microbiome, then, helps keep the body healthy. But that imbalance Mielcarz mentions has also been linked to a wide range of other conditions, includingacne, asthma and allergies, obesity, diabetes, eczema, cancer, and others. The challenge is that scientists are only beginning to understand the microbiome, and they don’t necessarily know what a “healthy” bacterial composition might be yet.
How Might MS and the Gut Microbiome Be Linked?
An imbalance in gut bacteria might set off alarm bells that lead the body to overreact and attack itself — causing autoimmune disease. Researchers cannot say for an absolute fact that the microbiome is linked to autoimmune disease, but more and more evidence is pointing in that direction.
“We know that MS is caused by a combination of genetic and environmental factors, but these are only partially understood,” says Ilana Katz Sand, MD, an assistant professor of neurology and associate medical director of the Corinne Goldsmith Dickinson Center for MS at Mount Sinai Hospital in New York City. “Most of the environmental contribution to MS remains unexplained.”
Given the interactions between gut microbiota and the immune system, it’s plausible “that certain microbes could improperly stimulate the immune system and contribute to MS,” Dr. Katz Sand says.
But there is still a lot to learn.
“Our knowledge about the connection between the gut microbiome and multiple sclerosis is still very limited,” Dr. Mazmanian says. “However, several groups are now studying whether the microbiome impacts MS in humans and mouse models.”
What the MS-Gut Research Shows
More and more studies are finding links between the microbiota in the gut and MS. Unpublished study results presented at the 2015 annual meeting of the American Academy of Neurology found differences in the bacterial composition of children with MS versus those without. Another study presented at the same meeting found reduced multiple sclerosis-like symptoms in mice when the mice were given yeast, and yet another study presented at the 2014 annual meeting found changes in the gut bacteria of people with MS when they had certain treatments.
Some studies in mice cannot be replicated in humans, says Mielcarz, but they’ve still revealed an important and surprising link between gut bacteria and the progression of central nervous system disease.
“We now have some early evidence in MS patients that certain bacteria that are thought to be pro-inflammatory are overrepresented, while others that are thought to be anti-inflammatory are underrepresented,” Katz Sand adds.
Researchers need to confirm these findings and then determine how they might influence clinical practice. To dig even more deeply into this area of research, a group of researchers from four different institutions formed the MS Microbiome Consortiumin 2013.
Does That Mean Gut Bacteria Are the Secret to Curing MS?
Almost certainly not. If gut bacteria are playing a role in MS, as scientists suspect and as evidence is suggesting, they’re not doing it all on their own. Several other factors have been linked to multiple sclerosis, such as smoking, vitamin D deficiency, and high sodium intake.
“As with any promising early research, there are sure to be less scrupulous people trying to sell MS treatments related to the gut microbiome that have not been subjected to rigorous clinical trials,” Mielcarz says.
He adds, “While there may at some point be effective therapeutics targeting the gut microbiota, as of now, anyone trying to sell something along those lines is doing something unproven at best — and dangerous at worst.”
What Comes Next for Multiple Sclerosis and the Gut?
Research is likely to head in two major directions, according to Mielcarz. One is “a more personalized approach in which the gut microbiome and genetic risk factors are analyzed together, potentially revealing subsets of MS patients that were previously unknown. The other is continuing to find and understand how gut microbiota influence immune functioning.”
“Over the next few years, we should be able to determine whether a person’s individual microbiome signature may be helpful as a diagnostic test for MS, as well as whether that signature has any prognostic value regarding disease severity going forward,” Katz Sand says. “We should also be able to discern whether the presence or absence of certain microbes predicts response to particular MS treatments.”
The goal is to find out whether medications or procedures, such as fecal transplants, can manipulate the microbiome to benefit patients with MS. Researchers will investigate how diet, antibiotics, probiotics, and prebiotics all affect the microbiome and its influence on multiple sclerosis.
“As of now, most research into the gut microbiome in MS is in the exploratory phase, with studies focusing on describing the microbiome of MS patients” compared to healthy people, Mielcarz says. While many of those studies appear to show a link between the microbiome and MS, it’s possible that those changes in the gut are a result of multiple sclerosis and not a cause of it.
Mielcarz adds, “It is difficult to predict timelines in the pharmaceutical business, but I would think it likely that a microbiome-modifying or microbiome-derived agent may enter clinical trials within the next five years.”