How gut microbiota changes the blood-brain barrier

Don’t be alarmed, but we are outnumbered. When figuring out what makes us, “us” we need to remember that there are far more bacteria genes in us than human genes, by recent counts it’s something like 360 to 1. We also know that your stomach can change your cravings, but now we know that your stomach affects more than just your thoughts. Your stomach can control what can get to your brain.

A new study in mice shows that our natural gut-residing microbes can influence the integrity of the blood-brain barrier, which protects the brain from harmful substances in the blood. According to the authors, the findings provide experimental evidence that our indigenous microbes contribute to the mechanism that closes the blood-brain barrier before birth. The results also support previous observations that gut microbiota can impact brain development and function.

So for those who need a refresher, the blood-brain barrier is a highly selective barrier that prevents unwanted molecules and cells from entering the brain from the bloodstream. In the current study the team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by gut microbes – which therefore play an important role in the protection of the brain.

The investigators reached this conclusion by comparing the integrity and development of the blood-brain barrier between two groups of mice: the first group was raised in an environment where they were exposed to normal bacteria, and the second (called germ-free mice) was kept in a sterile environment without any bacteria.

“We showed that the presence of the maternal gut microbiota during late pregnancy blocked the passage of labeled antibodies from the circulation into the brain parenchyma of the growing fetus”, says first author Dr. Viorica Braniste at the Department of Microbiology. “In contrast, in age-matched fetuses from germ-free mothers, these labeled antibodies easily crossed the blood-brain barrier and was detected within the brain parenchyma”.

The team also showed that the increased ‘leakiness’ or permeability of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this ‘leakiness’ could be repaired if the mice were exposed to fecal transplantation of normal gut microbes.

Unfortunately, the precise molecular mechanisms remain to be identified. However, the team was able to show that so-called tight junction proteins, which are known to be important for the blood-brain barrier permeability, did undergo structural changes and had altered levels of expression in the absence of bacteria.

According to the researchers, the findings provide experimental evidence that alterations of our indigenous microbiota may have far-reaching consequences for the blood-brain barrier function throughout life.

“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”, says Professor Sven Pettersson. “Given that the microbiome composition and diversity change over time, it is tempting to speculate that the blood-brain barrier integrity also may fluctuate depending on the microbiome. This knowledge may be used to develop new ways for opening the blood-brain-barrier to increase the efficacy of the brain cancer drugs and for the design of treatment regimes that strengthens the integrity of the blood-brain barrier”.

In certain sci-fi movies we see characters with a “hive mind,” or one mind for several separate entities. Maybe, just maybe, you and I are really an us. Maybe the things that make us “unique” are just millions of votes that go to an ultimate choice that we just think we have control over.

Maybe I’ve just watched one too many movies, but then again sometimes the truth is stranger than fiction.

Sources:

Viorica Braniste, Maha Al-Asmakh, Czeslawa Kowal, Farhana Anuar, Afrouz Abbaspour, Miklós Tóth, Agata Korecka, Nadja Bakocevic, Ng Lai Guan, Parag Kundu, Balázs Gulyás, Christer Halldin, Kjell Hultenby, Harriet Nilsson, Hans Hebert, Bruce T. Volpe, Betty Diamond, & Sven Pettersson (2014). The gut microbiota influences blood-brain barrier permeability in mice Science Translational Medicine : 10.1126/scitranslmed.3009759