Alterations in gut bacteria at a young age could help to trigger and progress multiple sclerosis in people who are genetically predisposed to the autoimmune disease.
A team of researchers from Rutgers-Robert Wood Johnson Medical School in Piscataway, NJ, came to this conclusion after studying the effect of altered gut bacteria in mice genetically engineered to have a high risk of multiple sclerosis (MS). They report their findings in the journal PNAS.
A significant feature of the new study is that it suggests a mechanism through which altered gut bacteria and MS risk genes — acting during young adulthood — may collaborate to trigger the disease. Another is that the researchers engineered a unique mouse model to study MS.
MS is a lifelong autoimmune disease wherein the immune system mistakenly attacks healthy tissue in the central nervous system (CNS), which comprises the brain, spinal cord, and optic nerves.
The immune attacks disrupt the nerve signals between the brain and the body that carry messages and help us to move our limbs and use our senses.
Clues on causes of MS increasing
There are many different symptoms of MS, depending both on which parts of the CNS come under attack and the extent of the damage.
These include: blurring and loss of vision; poor coordination and balance; tremors; extreme fatigue; numbness; slurred speech; paralysis; and difficulty concentrating and remembering. The symptoms can flare up and subside or they can stay and gradually get worse.
While MS can strike any person any age, most people are diagnosed between the ages of 20 and 50 and it is more common in women than in men.
In the United States, there is currently no formal consistent reporting of MS, but estimates suggest that there could be as many as 1 million people living with MS.
The exact causes of MS are still somewhat of a mystery, although scientists studying animal models of the disease have discovered many clues as to how the immune system and its inflammatory processes attack the myelin sheath and the nerve fibers inside.
'Gut dysbiosis' linked to MS
One area that researchers are homing in on is the role that gut microbes, or gut microbiota, might play in MS.
Alterations in the composition of the gut microbiota — termed "gut dysbiosis" — are often observed in people with MS, but the mechanisms through which they might be contributing to the disease are yet to be described.
To explore the role of gut dysbiosis in MS further, the Rutgers researchers genetically engineered a unique breed of mice so that they had a high risk of developing MS. They did this by inserting human genes known to be linked to MS into the mice.
The team — including Prof. Suhayl Dhib-Jalbut, director of Rutgers-Robert Wood Johnson Center for Multiple Sclerosis — found that if the genetically engineered mice were raised in a germ-free, sterile environment, "they did not develop MS."
However, when they moved the mice to a normal environment — that is, one that contains many types of bacteria — they found that the animals did develop symptoms that were very similar to human MS.
The mice also developed bowel inflammation, which suggested to the team that something to do with the gut bacteria might have triggered the MS-like disease.
Age, gut dysbiosis, and risk genes
The team also found that the younger mice were more likely to develop MS than the older mice, suggesting that there was an age-related window of opportunity for the altered gut bacteria and MS risk genes to collaborate and trigger the disease.
During that period in young adulthood of the mice, the researchers observed a reduction in the "development of Foxp3+ Treg cells and expression of E3 ubiquitin ligase genes involved in protection from autoimmune diseases."
The scientists therefore suggest that a direction for future study could be how to eliminate the harmful strains of bacteria or increase the beneficial strains to slow progression of MS. In their study, they identified some of these.
The team is already in receipt of funding to carry on their investigation in people with MS.
"The findings could have therapeutic implications on slowing down MS progression by manipulating gut bacteria."
Prof. Suhayl Dhib-Jalbut