T cells play a critical role in autoimmune diseases in the brain, particularly in multiple sclerosis (MS). Since T cells are normally prevented from crossing the blood–brain barrier (BBB), autoimmunity requires prior activation of naturally occurring autoreactive T cells in peripheral tissue. Recently, a critical role for the microbiota in this activation process has emerged. Here, we review the role of gut-associated lymphoid tissues (GALT) as a major site for the phenotypic changes that allow the migration of autoreactive T cells to the brain. Additionally, we examine the involvement of the microbiota in clinical MS as well as other brain disorders such as Parkinson’s disease (PD), stroke, and psychiatric disorders.
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