The Microbiome and MS
New Directions in MS Research: New Therapeutic Approaches
Over the past decade, it has become clear that interactions between a person’s microbiome and their 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. Specifically, researchers have hypothesized that imbalances in the number or types of different strains of bacteria could potentially cause the immune system to be inappropriately activated with autoimmune disease as the result.
Multiple groups presented research on the microbiome and its potential connection71 to MS in 2016. In one study, 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 less diversity, something that was reversed in the control group. In another study, investigators from the MS Microbiome Consortium presented their 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 basic72/experimental program and sequencing/bioinformatics program. The iMSMS has a goal of analyzing the microbiome of 2,000 MS patients and 2,000 healthy controls. They are also working with animal models.
Initial results from this group show significant differences in the microbiomes of patients treated with Copaxone compared to untreated subjects. 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.
Strikingly, when transferred into germ-free mice, gut microbiota from an individual with MS resulted in more severe EAE (an animal model of MS) than microbiota from a healthy control. This may be the most intriguing result from this project to date. Observed differences between cases and controls suggest a biological effect and warrant further investigation, as do effects of geographic, demographic, and dietary factors. Study of the human microbiome has the potential to yield important insights in understanding the basic processes underlying the disorder of MS as well as possible treatment strategies.
A separate study of microbiome in MS looked at differences in Vitamin D levels predicting alterations in gut bacteria. Analysis of 43 subjects showed increased abundance of a type of helpful bacteria called Ruminococcaceae in untreated MS patients with a serum Vitamin D level above 40 ng/ml, versus patients 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.