The Microbiome and MS
New Directions in MS Research: New Therapeutic Approaches
A growing body of research has documented how the interaction between an individual’s microbiome and immune cells may contribute to the development and severity of many disease states, including MS. The microbiome refers to the many millions of bacteria that reside in a person’s body, with current research focusing mainly on the bacteria that live in the intestines. Researchers have hypothesized that imbalances in the number or types of different strains of bacteria could cause the immune system to be inappropriately activated, with autoimmune diseases occurring as the result.
Some of the latest research in this area was presented at the October 2017 ECTRIMS-ACTRIMS Meeting. In one study, investigators gave the probiotic VSL3 to nine individuals with relapsing-remitting MS and 13 healthy controls. Seven of the people with MS were taking Copaxone® (glatiramer acetate); the other two were not taking a disease-modifying therapy. Study participants took two doses of the probiotic daily for two months. Stool samples from each subject were collected prior to the start of probiotic therapy, at discontinuation of probiotic therapy, and three months afterward. Blood samples were also collected to profile immune cells and immune gene expression.
Analysis of the stool samples showed that VSL3 induced changes in the composition and function of the bacteria in the gastrointestinal tract associated with an anti-inflammatory peripheral immune system response in both people with MS and healthy patients. Additionally, analysis showed decreased expression of pro-inflammatory genes in controls and increased expression of anti-inflammatory genes in people with MS following VSL3 administration.80 Although this is a small study that did not include clinical outcomes, it nonetheless raises the intriguing possibility of using probiotics in conjunction with other therapies to alter the course of MS.
In a study reported in 2016, a group of pediatric MS researchers analyzed the microbiome of a small group of children with pediatric MS versus control subjects. Although they were unable to find a characteristic bacteria “signature” that could identify the MS patients’ microbiomes compared to the controls, they did find that individuals with MS who had more types of bacteria in their microbiome had increased amounts of inflammatory immune cells in their blood compared to those with fewer types of bacteria, something that was reversed in the control group. In another study, investigators from the MS Microbiome Consortium presented work that demonstrated differences in the microbiome that correlated to whether a person was treated with an MS medication or not, and if treated, whether they were on an oral or injectable MS therapy.
The iMSMS (international MS Microbiome Study) is an international multi-disciplinary collaboration composed of researchers from the United States, England, and Argentina. Together, they have initiated a microbiome-oriented basic81 experimental program and sequencing/bioinformatics program. The iMSMS has a goal of analyzing the microbiome of 2,000 individuals with MS and 2,000 healthy controls. They are also working with animal models.
Initial results from this group show significant differences in the microbiomes of individuals treated with Copaxone compared to untreated participants. Women taking Copaxone showed significant enrichment of members of the Enterobacteriaceae family of bacteria, compared to gender-matched controls who were not taking Copaxone. Geographical differences were noted, as well.
Another study of the microbiome in MS looked at differences in Vitamin D levels predicting alterations in gut bacteria. Analysis of 43 participants showed increased abundance of a type of helpful bacteria called Ruminococcaceae in individuals with MS who were untreated and had a serum Vitamin D level above 40 ng/ml, versus individuals with a Vitamin D level below 40. The authors conclude that high levels of Vitamin D in untreated MS patients are associated with increased amounts of Ruminococcaceae in the gut. This has relevance to MS, as a decreased amount of Ruminococcaceae has previously been associated with Crohn’s disease. Hence, lower amounts of Ruminococcaceae might be linked to increased inflammation in MS. Further studies are underway to explain the mechanism by which Vitamin D regulates the composition of the microbiota in MS.