title: The gut microbiota influences blood-brain barrier permeability in mice.
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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden. viorica.braniste@ki.se sven.pettersson@ki.se.
authors.forename: Viorica
authors.initials: V
authors.lastname: Braniste
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Maha
authors.initials: M
authors.lastname: Al-Asmakh
authors.affiliation: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
authors.forename: Czeslawa
authors.initials: C
authors.lastname: Kowal
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Farhana
authors.initials: F
authors.lastname: Anuar
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Afrouz
authors.initials: A
authors.lastname: Abbaspour
authors.affiliation: Psychiatry Section, Department of Clinical Neuroscience, Karolinska Institutet, 17176 Stockholm, Sweden.
authors.forename: Miklós
authors.initials: M
authors.lastname: Tóth
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, 17177 Stockholm, Sweden.
authors.forename: Agata
authors.initials: A
authors.lastname: Korecka
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
authors.forename: Nadja
authors.initials: N
authors.lastname: Bakocevic
authors.forename: Lai Guan
authors.initials: LG
authors.lastname: Ng
authors.affiliation: Singapore Immunology Network, Agency for Science, Technology and Research, Singapore 138648, Singapore.
authors.forename: Ng Lai
authors.initials: NL
authors.lastname: Guan
authors.affiliation: Lee Kong Chian School of Medicine, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Parag
authors.initials: P
authors.lastname: Kundu
authors.affiliation: 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.
authors.forename: Balázs
authors.initials: B
authors.lastname: Gulyás
authors.affiliation: 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.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Department of Laboratory Medicine, Karolinska Institutet, 14186 Stockholm, Sweden.
authors.forename: Kjell
authors.initials: K
authors.lastname: Hultenby
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden.
authors.forename: Harriet
authors.initials: H
authors.lastname: Nilsson
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, and School of Technology and Health, KTH Royal Institute of Technology, Novum, SE-141 57 Huddinge, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Hebert
authors.affiliation: Laboratory of Functional Neuroanatomy, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
authors.forename: Bruce T
authors.initials: BT
authors.lastname: Volpe
authors.affiliation: Center for Autoimmune and Musculoskeletal Disease, The Feinstein Institute for Medical Research, North Shore-LIJ Health System, Manhasset, NY 11030, USA.
authors.forename: Betty
authors.initials: B
authors.lastname: Diamond
authors.affiliation: 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.
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D005260:Female; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D064307:Microbiota; D010539:Permeability; D011247:Pregnancy; D019108:Tight Junctions / Q000378:metabolism