Multiple sclerosis (MS) is the most common chronic inflammatory autoimmune disease of the central nervous system (CNS) and starts in young individuals in the most productive period of their lives. Its multifactorial pathogenesis includes genetic and environmental factors such as communication of the gut microbiota with peripheral and central immune processes. Accordingly, previous studies have demonstrated that commensal microorganism in the gut can modulate immunological processes both in the peripheral immune system as well as within the CNS and alterations in gut microbial composition have been identified as essential component of neuroinflammation. In this context, published and preliminary data from our groups suggest that microbial derived factors participate in the onset and progression of autoimmune CNS inflammation in MS. However, our mechanistic understanding of these processes is still limited. Within this project, we will dissect microbiota-gut-brain communication via bacterial-derived extracellular vesicles and determine how this interaction affects the CNS and MS related autoimmunity. The long-term vision of this project is to identify novel routes of microbiota-brain crosstalk that can be targeted for therapeutic approaches.