GUT-BRAIN connection: Exploring the role of Microbiome in Multiple Sclerosis

Multiple Sclerosis is an inflammatory demyelinating disorder of the Central Nervous System of debated etiology. While there is general consensus regarding the role of an active immune system in myelin destruction, the questions related to the initial events triggering immune system involvement remain unanswered and the identity of disease course modifiers is only partially understood. Epidemiological studies have suggested the possibility that disease onset and course are the result of an interaction between genetic susceptibility and environmental factors, though much remains to be learned about the identity of the environmental factors and whether they can be modified.  Among the proposed variables affecting MS are geographic location, smoking, vitamin D levels and the much debated diet and infections.

The ultimate goal  of the Casaccia’s Laboratory is to test the effect of environmental factor on epigenetic regulation of gene expression.   Diet is one of the best examples of environment-host interaction and the gastro-intestinal tract provides a large interface between environmental exposure and physiological responses.  In addition, genome-wide association studies on large MS patient populations have validated several SNPs  in common with diseases of the gastro-intestinal (GI) tract, including celiac disease, Crohn’s disease, or ulcerative colitis. Together these data suggest the possibility that the GI tract may play a similar role in these different diseases, possibly as an intermediary step between the environment and the immune system of the host.

The actual cross-talk between dietary intake and host immune system however is not direct, but rather mediated by the commensal bacteria residing in the walls of the intestine and collectively termed the “microbiome”.  These bacteria can be classified by taxonomy based on the unique DNA sequences of distinct phyla.  They have been shown to be responsive to dietary manipulations and play a critical role in regulating metabolism, nutrient absorption and modulation of peripheral immune system activity.   The importance of the intestinal microbiome and its interactions with the immune system are being increasingly recognized with regard to the development of autoimmune diseases.   Links have already been demonstrated in inflammatory bowel disease, type 1 diabetes, ,  and rheumatoid arthritis.

In addition, several studies have demonstrated this link in preclinical models of MS even though no studies have been published in MS patients to date. In collaboration with Dr. Ilana Katz-Sand and the staff and clinical neurologists at  the Corinne Goldsmith Center for Multiple Sclerosis Research and Treatment, we have started recruiting MS patients to test the hypothesis that specific microbiota identify well characterized populations of MS patients. The successful completion of these experiments, will allow us to move towards our long-term goal to implement a much larger research project, aimed at studying the effect of diet on the microbiome and disease course in MS patients.

2 thoughts on “GUT-BRAIN connection: Exploring the role of Microbiome in Multiple Sclerosis

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    Stephen Warren

    October 15, 2014 at 10:33pm

    Interestingly it is now thought that Parkinson’s Disease may well start in the gut
    (http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012728#s1). This is because α-synuclein, a protein whose misfolding seems to be associated with PD, is first found in the gut. Separately it has been proposed that PD is an auto immune disease (http://nwpf.org/stay-informed/news/2014/04/is-parkinsons-an-autoimmune-disease-neurons-may-die-from-bodys-faulty-immune-system/)

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    Robert Duncan

    November 15, 2014 at 5:03pm

    Where can I see a copy of the results of microbiome survey of diagnosed multiple sclerosis people and what items are common, and rare?

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