Importance of Microbiota in MS Development Explored in ECTRIMS 2015 Presentation

Three parallel sessions concerning multiple sclerosis (MS) prevention, clinical phenotypes and magnetic resonance imaging (MRI) were featured at the 31st Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), recently held in Barcelona, Spain (October 7 – 10, 2015). The first parallel session was entitled “Will MS be prevented?” and included six presentations on the subject.

Prof. Reinhard Hohlfeld from the Max-Planck-Institute of Neurobiology in Munich, Germany presented his work at the session under the title “Modulating microbiota: friend or foe.”

According to Prof. Hohlfeld, the risk for developing multiple sclerosis (MS) is influenced by both genetic and environmental factors. In a provocative question to the audience, Prof. Hohlfeld said, “Is MS really a primary degenerative disease? Animal models may say otherwise.”

Studies using a mouse model of human MS – the spontaneous experimental autoimmune encephalomyelitis (EAE) mouse model — revealed that the gut microbiome (microbiota; the community of microorganisms present in the gut) plays an important role in MS development. In fact, germ-free animals (without microbiota) do not develop EAE, while these particular animals under a “normal” bacterial environment spontaneously develop the disorder. “Spontaneous EAE depends on the bacterial microbiome” stated Prof. Hohlfeld.

Based on this observation, it has been suggested that the autoimmune reaction against the tissue in the central nervous system seen in MS patients might be remotely controlled by the gut microbiota. Interestingly, as Prof. Hohlfeld pointed out in his talk, the microbiota is known to influence the gut-associated lymphoid tissue (GALT), and in turn, the GALT is known to regulate the systemic immune system.

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The exact role of microbiota in MS, however, remains poorly understood. To address this question, approaches based on novel DNA sequencing techniques and bioinformatics have been developed in order to analyze complex bacterial “metagenomes.” Through these approaches, it might be possible to identify individual microbiota profiles that are linked to an increase or decreased in the risk of developing MS. Such putative microbial-associated biomarkers may offer new therapeutic strategies for the prevention and treatment of MS.

According to Prof. Hohlfeld, “Something happens in the gut vicinity, the T cells have to be activated in the gut milieu before they can make it to the brain”. Since the microbiota is responsible for inducing the maturation of the gut-associated lymphoid system [GALS], then the microbiota comes into close contact with immune cells. On these events, bacterial products might be taken up by specific cells (antigen-presenting cells, APC) and introduced into lymph nodes. The immune “B and T cells mature in these gut-associated lymphoid tissues, and migrate into the blood stream and systemic circulation” explained Prof. Hohlfeld, “Different bacteria induce different T cells. The GALS significantly contributes to the education of the immune system.”

Prof. Hohlfeld provocatively set forth this challenge: “Can microbiome research help to prevent MS? The power of Poop?” concluding, “We need to understand the properties and disease associations of the human microbiota. The microbiota should be incorporated into MS trials and study design.”