A Multidisciplinary Approach to Study the Role of the Gut Microbiome in Relapsing and Progressive MS
Abstract
Scientific Objective and Rationale: Multiple sclerosis (MS) is a complex disease involving genetic and environmental susceptibility factors. While a great proportion of the genetics of MS has been already discovered, much less is known about the environmental variables possibly triggering this disease. The human body is inhabited by a vast number of bacteria, archaea, viruses, and unicellular eukaryotes (collectively known as the microbiota). This microbial community interacts with the host and the environment and creates an extremely complex ecosystem, termed the microbiome. This ecosystem is particularly heterogeneous in the gut, comprising a community of 10^13-14 organisms in the most densely populated lower gastrointestinal (GI) tract (10-100 times more numerous than human cell numbers). It has also been shown that changes in the microbial composition of the intestinal compartments modify the normal functioning of the immune system and can have profound effects on how the human body reacts to the surrounding environment. We believe that the gut of MS patients harbors a significantly different set of bacteria than that of healthy individuals. More specifically, we also think that gut bacteria from subjects with primary progressive MS is different from that of subjects with relapsing disease. We will use the latest advances in DNA sequencing technologies to investigate these important questions. Applicability: A positive outcome of this investigation will pave the road to develop novel therapies, based on restoring the normal microbiota. This may also result in the first class of therapies effective in progressive forms of MS. A possible outcome of this study is that we discover that restoring one or a few bacterial communities has a beneficial effect in the progression of MS. We envision these new therapies will be based on supplementation of missing communities by probiotics (live bacteria) or stimulation of their presence by prebiotics (natural compounds that allows growth of specific bacteria). Since these potential therapeutic approaches aim at modifying the existing gut microflora with probiotics or prebiotics, the associated risk to the patient is very low. While these are likely scenarios in the near to mid-term future, this is a new field of research and more basic studies need to be completed to adequately guide development of these novel kind of therapeutics. The present proposal represents a solid step towards this goal.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Apr 04, 2016
- Source ID
- W81XWH1510652
Entities
People
- Sergio E Baranzini
Organizations
- United States Army
- University of California, San Francisco