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Sci Transl Med. 2014 Nov 19;6(263):263ra158. doi: 10.1126/scitranslmed.3009759.

The gut microbiota influences blood-brain barrier permeability in mice.

Author information

1
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. viorica.braniste@ki.se sven.pettersson@ki.se.
2
Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
3
Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
4
Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden.
5
Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
6
Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
7
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.
8
Department of Laboratory Medicine, Karolinska Institutet, 14186 Stockholm, Sweden.
9
Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden.
10
Laboratory of Functional Neuroanatomy, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
11
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.

Erratum in

  • Sci Transl Med. 2014 Dec 10;6(266):266er7. Guan, Ng Lai [corrected to Ng, Lai Guan].

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.

PMID:
25411471
PMCID:
PMC4396848
DOI:
10.1126/scitranslmed.3009759
[Indexed for MEDLINE]
Free PMC Article

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