An intact blood–brain barrier (BBB) is vital for regulating the exchange of nutrients and molecules between the circulatory system and the brain parenchyma. Viorica Braniste and colleagues found that germ-free mice displayed increased BBB permeability compared with pathogen-free mice with normal gut microbiota. Exposure of the germ-free mice to a pathogen-free gut microbiota decreased BBB permeability and upregulated the expression of tight junction proteins.