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Multiple sclerosis (MS) is an inflammatory disease of the central nervous system driven by autoreactive lymphocytes. Due to its close contact with the gut-associated lymphoid tissue, the intestinal microbiota and/or their metabolites may be one of the factors that influence the activation of autoreactive lymphocytes. This article summarizes and discusses the current research efforts to characterize the microbiome of MS patients using human material. In addition, we present research studies that utilized classical or humanized animal models to determine the influence of certain microbiota species or compositions of microbiota on the immune system and disease progression and to define possible causal associations.