The Microbiome and MS
New Directions in MS Research: New Therapeutic Approaches
The vast collection of organisms that inhabit the human gut, the microbiome, has been demonstrated to influence immune responses and modulate susceptibility to chronic diseases. Recent studies have related gut dysbiosis (an imbalance of bacteria) to Crohn’s disease, type 1 diabetes, obesity, and autism. Additionally, animal model work suggests an important role in MS.
The Multiple Sclerosis Microbiome Consortium (MSMC) is a multi-disciplinary collaboration composed of two translational MS Centers (Mount Sinai and UCSF). Together, they have initiated a microbiome-oriented basic/experimental program and sequencing/ bioinformatics program. The MSMC is currently analyzing hundreds of samples by bacterial DNA sequencing aimed at identifying group differences at the genus-level (a genus is a group of related animals or plants that includes several or many different species66). Tracked variables include demographics, body mass index (BMI), medical history, MS clinical course and phenotype, disease-modifying therapy, and diet. The MSMC has successfully implemented IRB-approved protocols to recruit MS patients and controls, as well as to process and analyze their blood and stool samples.
Initial results show significant genus-level differences in the microbiomes of patients treated with Copaxone compared to untreated subjects. Female patients 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 MS patient 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.