One of the major efforts currently being explored to understand the immune system in health and disease is investigation of the human microbiome. Numerous studies in animal models of MS implicate the microbiota of the gut in triggering CNS autoimmunity. We have had a long-term interest in the gut immune system and we reembarked on a pilot study to determine if differences in the gut microbiome existed in MS patients and whether any changes in the gut microbiome occurred in association with treatment. We found a significant increase in abundance of organisms from the Archaea kingdom in MS and changes in the gut microbiome associated with treatment. To our knowledge, this is the first demonstration of changes in the gut microbiome in MS. The focus of our investigations are to expand the numbers of patients studied, include patients with the progressive form of the disease, to study patients in a longitudinal fashion before and after treatment, and to perform immunologic investigations to understand the manner in which Archaea affects immune function in MS. We hypothesize that changes in the gut microbiome are linked to susceptibility and immune changes that occur in MS as well as response to treatment.
Aim 1. Investigate the gut microbiome in untreated MS subjects including CIS, relapsing- remitting and secondary progressive MS.
Aim 2. Investigate the effect of treatment on the gut microbiome in MS.
Aim 3. Investigate the linkage of Archaea in the gut microbiome of MS patients to immune function. To perform our studies, we will take advantage of the large cohort of well characterized MS patients followed at the Partners MS Center as part of the CLIMB longitudinal observational study and the Center for Clinical and Translational Metagenomics at the Brigham and Women's Hospital.

Public Health Relevance

It is now known that the gut is a very important part of the immune system. We will investigate changes in the gut flora in MS patients. This provides the opportunity to better understand the cause of MS and develop new therapies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS087226-01A1
Application #
8818784
Study Section
Clinical Neuroimmunology and Brain Tumors Study Section (CNBT)
Program Officer
Utz, Ursula
Project Start
2014-09-30
Project End
2019-07-31
Budget Start
2014-09-30
Budget End
2015-07-31
Support Year
1
Fiscal Year
2014
Total Cost
$387,096
Indirect Cost
$168,346
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115