Multiple sclerosis (MS), an inflammatory and demyelinating autoimmune disease has both a genetic and an environmental predisposition. MHC class II region on chromosome 6 accounts for majority of familial clustering in MS. Among the potential environmental factors, microbes and particularly gastrointestinal (GI) bacteria have been suggested to play an essential role in the etiopathogenesis of MS. The human GI track contains enormous (1014) population of microorganism. Despite the vast microbial burden and the close contact between the microbes and host, commensal intestinal microbiota are considered to be beneficial. The interaction of the intestinal microbes with the innate immune system might be a critical epigenetic factor modifying inflammatory and autoimmune diseases such as MS. This hypothesis is further supported by recent findings that levels of certain commensal bacteria such as Prevotella species and bifidobacterium are decreased in stool of patients of rheumatoid arthritis and Crohn?s disease.
While much is known about the genetic and environmental triggers for MS, our understanding of the disease is incomplete, in particular, there are important questions which need to be addressed.
1. What is the composition of fecal microbiota of MS patients and if it differ from fecal microbiota of healthy control? The differences in the composition of intestinal microbiota and in the function of immune system might determine which patients get MS. In addition, detail fecal microbiota analysis might lead to identification of bacteria that negatively correlate with the autoimmune state and prove to be useful as a potential therapeutic target.
2. If the fecal microbiota in MS patients is influenced by MHC genotype of individual? Of note the host genotype appears to affect the composition of the microbiota. MHC genes responsible for modulation of the immune system and affecting the risk of MS might also guide the composition of intestinal microbiota.
Selection of Volunteers: Multiple Sclerosis: ● Neurologist physician will identify the cases of MS in special MS clinics and will contact the study coordinator if potential patients are identified. ● Review Preparatory to Research (RPR) has been completed for permission to access to physician calendars. ● We plan to will recruit 100 subjects into this study either in person or by mail. Healthy Volunteers: ● Healthy volunteers will not be recruited. Healthy control data will be used for comparison from the nationally published Human Microbiome Project (HMP), National Institutes of Health.
Inclusion criteria ● Cases of MS (any number years of disease duration) ● Both Relapsing-remitting as well as primary progressive case of MS
Exclusion criteria ● Patients taking antibiotics, laxative, probiotics ● Patients who recently have had a colonoscopy or similar procedure
To collect stool and blood samples from patient with S and compare the fecal microbiota of patients with MS to healthy control. Blood samples will used for HLA genotyping and sera collection for antibody analysis. This resource will be invaluable in answering the important questions outlined above and other future unanswered questions.
Bacterial DNA will be isolated from Stool samples using standard protocol. Fecal micobiota will be examined based on an average 4,396 16S rRNA amplicon at Mayo Core facility and data will be analyzed at Biomedical informatics division at Mayo. HLA genotyping will be done using standard PCR amplification utilizing sequence ?specific primers.
A one time stool and blood sample would be collected.
Last updated: 12/05/2012