MS scientific literature is fascinating. Few neurological (and non-neurological) diseases can compete in number of papers, impact factor and mainstream media attention. However many research projects use classical animal models (experimental allergic encephalmyelitis, EAE) and those animal models have been an enormous source of erroneous extrapolations to MS pathogenesis. Many times the EAE model has been a research target itself and not because the results it could provide truly matched with what we want to know about MS. However, despite the noise that animal models generate, it must be aknowledged that they have evolved into more accurate models and have boosted MS research and knowledge. I like the “from bedside to bench” approach and not the other way round but, sometimes, basic research works initiate breakthrough hypothesis that deserve “bedside” research.

I bring up this statement after reading the paper Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination by Kerstin Berer and co-workers and published in Nature in October 2011. The hypothesis is beautiful (but not new) and, although it probably needed a lot of experiments and comprobations, methods are pretty simple. They used a mouse model of spontaneous relapsing remitting MS, in which CD4 T cells constitutively express a T cell receptor that recognizes myelin oligodendrocyte glycoprotein peptides. They start with the observation that this model develops MS in variable proportions depending on the research group using the model. Then they wondered if the way these mice were bred had any influence in encephalomyelitis development and bred them in two different conditions: a conventional pathogen free (or SPF) environment or in a complete germ-free environment. In SPF breeding commensal microbiota can grow and animals are only pathogen-free. In germ-free environment animals don’t have commensal microbiota. The main goal was to see if there were differences in MS rates between both groups. And eureka!: none of the animals bred in germ-free environment developed EAE while 80% of SPF-bred animals developed EAE at 30 days. Moreover, when germ-free animals were recolonized with microbiota developed EAE at the same rate and frequency as SPF-bred animals. The study then describes a number of immunological tests to confirm that the observation is due only to the breeding variable and not to factors related to the nature of the model or to complete T cell anergy due to germ-free conditions.

The main conclusion is that non-pathogenic bacterial microbiota may contribute to MS development. Or, more accurately, that autoreactive lymphocytes are necessary, but not sufficient, condition to develop MS. However, again, EAE is not MS, and human nature is much more varied and genetic discordant than lab mice. But taking in account that we know that genetic causes are not sufficient to develop MS and environmental factors play a decissive role, further research and, importantly, further colaboration, for example, between the MS genetics research consortium ( International MS Genetics Consortium) and microbiome research consortium (The Human Microbiome Project) is needed to explore in humans what this beautiful and simple study reports in mice.

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