The gut microbiota influences blood-brain barrier permeability in mice

Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). W...

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Published in	Science translational medicine Vol. 6; no. 263; p. 263ra158
Main Authors	Braniste, Viorica, Al-Asmakh, Maha, Kowal, Czeslawa, Anuar, Farhana, Abbaspour, Afrouz, Tóth, Miklós, Korecka, Agata, Bakocevic, Nadja, Ng, Lai Guan, Guan, Ng Lai, Kundu, Parag, Gulyás, Balázs, Halldin, Christer, Hultenby, Kjell, Nilsson, Harriet, Hebert, Hans, Volpe, Bruce T, Diamond, Betty, Pettersson, Sven
Format	Journal Article
Language	English
Published	United States 19.11.2014
Subjects	Animals Blood-Brain Barrier Female Intestines - microbiology Mice Microbiota Permeability Pregnancy Tight Junctions - metabolism
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Abstract	Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.
AbstractList	Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules and nutrients between the circulatory system and the brain parenchyma. The BBB also ensures homeostasis of the central nervous system (CNS). We report that germ-free mice, beginning with intrauterine life, displayed increased BBB permeability compared to pathogen-free mice with a normal gut flora. The increased BBB permeability was maintained in germ-free mice after birth and during adulthood and was associated with reduced expression of the tight junction proteins occludin and claudin-5, which are known to regulate barrier function in endothelial tissues. Exposure of germ-free adult mice to a pathogen-free gut microbiota decreased BBB permeability and up-regulated the expression of tight junction proteins. Our results suggest that gut microbiota-BBB communication is initiated during gestation and propagated throughout life.
Author	Diamond, Betty Halldin, Christer Volpe, Bruce T Tóth, Miklós Guan, Ng Lai Abbaspour, Afrouz Kowal, Czeslawa Ng, Lai Guan Braniste, Viorica Gulyás, Balázs Anuar, Farhana Hebert, Hans Korecka, Agata Nilsson, Harriet Kundu, Parag Al-Asmakh, Maha Bakocevic, Nadja Pettersson, Sven Hultenby, Kjell
Author_xml	– sequence: 1 givenname: Viorica surname: Braniste fullname: Braniste, Viorica email: viorica.braniste@ki.se, sven.pettersson@ki.se organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. viorica.braniste@ki.se sven.pettersson@ki.se – sequence: 2 givenname: Maha surname: Al-Asmakh fullname: Al-Asmakh, Maha organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden – sequence: 3 givenname: Czeslawa surname: Kowal fullname: Kowal, Czeslawa organization: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA – sequence: 4 givenname: Farhana surname: Anuar fullname: Anuar, Farhana organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden – sequence: 5 givenname: Afrouz surname: Abbaspour fullname: Abbaspour, Afrouz organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden – sequence: 6 givenname: Miklós surname: Tóth fullname: Tóth, Miklós organization: Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden – sequence: 7 givenname: Agata surname: Korecka fullname: Korecka, Agata organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden – sequence: 8 givenname: Nadja surname: Bakocevic fullname: Bakocevic, Nadja organization: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore – sequence: 9 givenname: Lai Guan surname: Ng fullname: Ng, Lai Guan – sequence: 10 givenname: Ng Lai surname: Guan fullname: Guan, Ng Lai organization: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore – sequence: 11 givenname: Parag surname: Kundu fullname: Kundu, Parag organization: Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore – sequence: 12 givenname: Balázs surname: Gulyás fullname: Gulyás, Balázs organization: Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden. Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore – sequence: 13 givenname: Christer surname: Halldin fullname: Halldin, Christer organization: Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden. Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore – sequence: 14 givenname: Kjell surname: Hultenby fullname: Hultenby, Kjell organization: Department of Laboratory Medicine, Karolinska Institutet, 14186 Stockholm, Sweden – sequence: 15 givenname: Harriet surname: Nilsson fullname: Nilsson, Harriet organization: Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden – sequence: 16 givenname: Hans surname: Hebert fullname: Hebert, Hans organization: Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden – sequence: 17 givenname: Bruce T surname: Volpe fullname: Volpe, Bruce T organization: Laboratory of Functional Neuroanatomy, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA – sequence: 18 givenname: Betty surname: Diamond fullname: Diamond, Betty organization: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA – sequence: 19 givenname: Sven surname: Pettersson fullname: Pettersson, Sven email: viorica.braniste@ki.se, sven.pettersson@ki.se organization: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. Singapore Centre on Environmental Life Sciences Engineering (SCELSE), Nanyang Technological University, Singapore 637551, Singapore. viorica.braniste@ki.se sven.pettersson@ki.se
BackLink	https://www.ncbi.nlm.nih.gov/pubmed/25411471$$D View this record in MEDLINE/PubMed
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Snippet	Pivotal to brain development and function is an intact blood-brain barrier (BBB), which acts as a gatekeeper to control the passage and exchange of molecules...
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SubjectTerms	Animals Blood-Brain Barrier Female Intestines - microbiology Mice Microbiota Permeability Pregnancy Tight Junctions - metabolism
Title	The gut microbiota influences blood-brain barrier permeability in mice
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