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   Gut microbiota influences blood-brain barrier permeability   
      
      
       
   7 hours ago   
      
   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 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, 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 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, 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 blood-brain barrier".   
      
       
   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/d   
   i/10.1126/scitranslmed.3009759   
      
   Provided by Karolinska Institutet   
      
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   http://m.medicalxpress.com/news/2014-11-gut-microbiota-blood-bra   
   n-barrier-permeability.html    
       
      
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