Gut microbiota influences blood-brain barrier permeability

November 19, 2014, Karolinska Institutet
Healthy gut microbiota may influence the early development of the blood-brain barrier. Credit: V. Altounian/Science Translational Medicine

A new study in mice, conducted by researchers at Sweden's Karolinska Institutet together with colleagues in Singapore and the United States, 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.

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, being published in the journal Science Translational Medicine, the international interdisciplinary research team demonstrates that the transport of molecules across the blood-brain barrier can be modulated by - 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, Tumor and Cell Biology at Karolinska Institutet. "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' of the blood-brain barrier, observed in germ-free mice from early life, was maintained into adulthood. Interestingly, this 'leakiness' could be abrogated if the mice were exposed to fecal transplantation of normal gut microbes. 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 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, the principal investigator at the Department of Microbiology, Tumor and Cell Biology. "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 ".

Explore further: Biotech company develops way to carry antibodies across blood-brain barrier to treat Alzheimer's

More information: 'The gut microbiota influences the blood brain barrier permeability in mice', Viorica Braniste, Maha Al-Asmakh, Czeslawa Kowa, Farhana Anuar, Afrouz Abbaspour, Miklos Toth, Agata Korecka, Nadja Bakocevic, Ng Lai Guan, Parag Kundu, Balazs Gulyas, Christer Halldin, Kjell Hultenby, Harriet Nilsson, Hans Hebert, Bruce T. Volpe, Betty Diamond, Sven Pettersson, Science Translational Medicine, online 19th November 2014. stm.sciencemag.org/lookup/doi/ … scitranslmed.3009759

Related Stories

Biotech company develops way to carry antibodies across blood-brain barrier to treat Alzheimer's

November 6, 2014
(Medical Xpress)—A team of researches with the biotech firm Genentech Inc has found a way to carry an antibody across the blood-brain barrier using transferrin in a monkey. In their paper published in the journal Science ...

Why inflammation leads to a leaky blood-brain barrier: MicroRNA-155

June 2, 2014
Until now, scientists have not known exactly how inflammation weakens the Blood-Brain Barrier, allowing toxins and other molecules access to the brain. A new research report appearing in the June 2014 issue of The FASEB Journal ...

New knowledge about the brain's effective bouncer

July 16, 2014
Research from the University of Copenhagen is shedding new light on the brain's complicated barrier tissue. The blood-brain barrier is an effective barrier which protects the brain, but which at the same time makes it difficult ...

Blood vessel growth in the brain relies on a protein found in tumor blood vessels

October 27, 2014
Do blood vessels that feed tumors differ from other blood vessels? Fourteen years ago, experiments designed to answer that question led to the discovery of several genes that are more active in tumor-associated blood vessels ...

Team moves small-molecule drugs through blood-brain barrier

June 4, 2014
Researchers at Mayo Clinic have demonstrated in a mouse model that their recently developed synthetic peptide carrier is a potential delivery vehicle for brain cancer chemotherapy drugs and other neurological medications. ...

New molecule sneaks medicines across the blood/brain barrier

October 30, 2014
Delivering life-saving drugs across the blood-brain barrier (BBB) might become a little easier thanks to a new report published in the November 2014 issue of The FASEB Journal. In the report, scientists describe an antibody, ...

Recommended for you

Japanese team creates human oogonia using human stem cells in artificial mouse ovaries

September 21, 2018
A team of researchers with members from several institutions in Japan has successfully generated human oogonia inside of artificial mouse ovaries using human stem cells. In their paper published in the journal Science, the ...

A new approach to developing a vaccine against vivax malaria

September 21, 2018
A novel study reports an innovative approach for developing a vaccine against Plasmodium vivax, the most prevalent human malaria parasite outside sub-Saharan Africa. The study led by Hernando A. del Portillo and Carmen Fernandez-Becerra, ...

A Trojan Horse delivery for treating a rare, potentially deadly, blood-clotting disorder

September 21, 2018
In proof-of-concept experiments, University of Alabama at Birmingham researchers have highlighted a potential therapy for a rare but potentially deadly blood-clotting disorder, TTP. The researchers deliver this therapeutic ...

Researchers explore how changes in diet alter microbiome in artificial intestine

September 21, 2018
Using an artificial intestine they created, researchers have shown that the microbiome can quickly adapt from the bacterial equivalent of a typical western diet to one composed exclusively of dietary fats. That adaptation ...

Study identifies stem cell that gives rise to new bone and cartilage in humans

September 20, 2018
A decade-long effort led by Stanford University School of Medicine scientists has been rewarded with the identification of the human skeletal stem cell.

Scientists grow human esophagus in lab

September 20, 2018
Scientists working to bioengineer the entire human gastrointestinal system in a laboratory now report using pluripotent stem cells to grow human esophageal organoids.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.