(Or It Takes Guts to Alter the Brain Part III)
The lastest gut-brain posts have focused on the role of the vagus nerve in gut-brain interactions. The vagus nerve runs from the brain into the abdomen and may serve as an important neural interface between the gut microbiota and the central nervous system. This post examines another physical component of the gut microbiota-brain axis. Unlike the vagus nerve, this structure does not provide a link between bugs and brain, but rather acts (primarily!) as a barrier. The blood brain barrier (or BBB) is composed of tightly-linked brain cells. Proteins, primarily claudins and occludins, stitch these cells together, forming tight junctions. The BBB allows water and certain molecules to pass from the blood into the brain, while preventing the transport of harmful substances, including bacterial components.
A recent study from the Pettersson Lab examined the role of the microbiota in BBB formation and maintenance*. Researchers found that germ-free mice (lacking a microbiota) exhibited increased BBB permeability. Remember, the BBB acts as the ultimate brain bouncer-protecting our nervous system from toxic substances. Disrupting BBB permeability may significantly impair brain health and function.
To measure BBB permeability, researchers injected [11C]raclopride, a radioactive substance, into the bloodstream of both germ-free mice and conventionally-raised mice. Used in tracer amounts, [11C]raclopride does not harm the brains or health of the mice. Following injection, positron emission tomography (PET) imaging was used to track the radioactive substance. Germ-free mice had a higher uptake of [11C]raclopride within the brain compared to conventionally-raised mice. In addition, important tight junction proteins (occludin and claudin-5) were decreased in the brains of germ-free mice.
But could a gut microbiota fix the dysfunctional BBB? And if so, how?! To examine the role of the microbiota in BBB formation, researchers colonized germ-free mice with the microbes from the gut microbiota of conventionally-raised mice. The previously germ-free mice exhibited decreased BBB permeability and increased levels of occludin and claudin-5. Next, researchers gave germ-free mice short-chain fatty acids (SCFAs), small molecules produced by gut microbes. Even without the microbes themselves, SCFA-treatment decreased BBB permeability. While the effects of increased BBB permeability in germ-free mice remains poorly understood, this study demonstrates another complex interaction between the gut microbiota and brain health.
Stay tuned for upcoming posts on microbially-produced components (SCFAs, neurotransmitters, and more!) involved in the gut microbiota-brain axis.
Sources + Additional Information:
Pettersson Lab: http://ki.se/en/mtc/sven-pettersson-group