MS involves immune-system attacks against the brain and spinal cord. The gut, including the small and large intestine, is the largest immune organ in mammals. Each of us has millions of “commensal” bacteria living within our guts. Most of these bacteria are harmless as long as they remain in the inner wall of the intestine. They play a critical role in our normal physiology, and accumulating research suggests that they are critical in the establishment and maintenance of immune balance by the molecules they release. The MS Microbiome Consortium was created in 2013 by the investigators participating in this proposal. Its members have world-class expertise in genomics (Dr. Sergio Baranzini), clinical care and research (Drs. Bruce Cree, UCSF, and Ilana Katz-Sand, Mount Sinai School of Medicine), microbiology (Dr. Sarkis Mazmanian, California Institute of Technology), and neuroscience (Dr. Patrizia Casaccia, Mount Sinai School of Medicine). Dr. Rob Knight (University of California San Diego) new to the field of MS research, pioneered the development of advanced computational methods for identifying microbial species. The consortium is performing a comprehensive micro biome analysis in MS. Specifically, we are comparing the gut bacteria of people with relapsing MS, people with primary progressive MS, and healthy controls. We hypothesize that significant differences in gut bacteria exist among these groups that may drive MS progression. These findings will help the Consortium toward the goal of developing biomarkers of MS progression, as well as novel therapeutic approaches based on personalized probiotics.