The blood–brain barrier is a selectively permeable barrier between the brain extracellular fluid and the blood formed by capillary endothelial cells connected by tight junctions. The blood–brain barrier prevents potentially harmful molecules and cells from entering the brain and maintains microenvironmental conditions suitable for neuron growth. Its integrity is therefore crucial to proper brain function. A recently published article (Sci. Transl. Med. 6, 263ra158; 2014) identifies a surprising regulator of the integrity of the blood–brain barrier: the microorganisms that colonize the gut.

The study involved two groups of mice: one that had never been exposed to live bacteria (bacteria-free) and one that was kept in an environment that excluded commonly monitored mouse pathogens but had normal gut microbial communities (pathogen-free). Permeability of the blood–brain barrier in mice of both groups was examined during embryonic development and into adulthood. In fetal mice from bacteria-free mothers, the blood–brain barrier was more permeable than in those from pathogen-free mothers at the same stage of development. Increased blood–brain barrier permeability persisted after birth and during adulthood in mice raised in the absence of bacteria and was associated with dysregulation of tight junctions. Exposure of adult bacteria-free mice to fecal microbiota from adult pathogen-free mice restored the integrity of the blood–brain barrier.

The results show that communication between the gut microbiota and the brain is established during embryonic development and continues throughout life. Sven Pettersson (Karolinska Institute, Stockholm, Sweden), one of the senior authors of the report, said in a press release, “These findings further underscore the importance of the maternal microbes during early life and that our bacteria are an integrated component of our body physiology.”

The mechanisms that underlie gut–brain signaling and enable regulation of the blood–brain barrier by gut microbes are not yet known, nor are the consequences of increased permeability of the blood–brain barrier. The study's authors suggest that more physiological data are needed to confirm the findings and guide their interpretation. Regarding future applications of this work, Pettersson says, “This knowledge may be used to develop new ways for opening the blood–brain barrier to increase the efficacy of...drugs and for the design of treatment regimes that strengthen the integrity of the blood–brain barrier.”