Tuesday, 30 December 2014

Gut microbes and the blood-brain barrier

Gut microbes appear to influence the development of the blood-brain barrier in mice, before and soon after they’re born, according to a study published in Science Translational Medicine.

“It’s absolutely fascinating to think that gut bacteria can control permeability of the blood-brain barrier,” Caltech microbiologist Sarkis Mazmanian, who was not involved in the study, told The Scientist.

The blood-brain barrier (BBB), which shields the organ from blood-borne infections, toxins, and more, is created by steadfast connections called tight junctions between the endothelial cells that line its blood vessels. So effective is the barrier that most proteins and molecules cannot pass through; those that do generally require selective transport via specific receptors.

A similar barrier—made up of epithelial cells and tight junctions—lines the intestine and stops the trillions of microbes present in the gut from escaping into the body. It’s known that the gut bacteria themselves control integrity of this intestinal barrier, said Sven Pettersson of the Karolinska Institute in Sweden who led the new study.

The team compared development of the BBB between germ-free fetal mice and those with normal microbiomes. As expected, the mice with normal microbiomes exhibited normal closure of the BBB toward the late stages of fetal development—a traceable antibody that could be detected readily entering the brain in the early fetus became restricted to blood vessels later on. In the fetuses whose mothers were germ-free, however, the antibody continued to enter brain tissue even late in pregnancy.

This increased barrier permeability was associated with low expression and disorganization of tight junction proteins and was shown by additional methods to persist into adult life. That is, pups that were born to germ-free mothers and that remained germ-free throughout life had leakier BBBs as adults.

Reference:

V. Braniste et al., “The gut microbiota influences blood-brain barrier permeability in mice,”Science Translational Medicine, 6:263ra158, 2014.


Posted by Tim Sandle