title: Commensal microbiota modulate murine behaviors in a strictly contamination-free environment confirmed by culture-based methods.
abstract: BACKGROUND
  There is increasing evidence suggesting the existence of an interaction between commensal microbiota, the gut and the brain. The aim of this study was to examine the influence of commensal microbiota on the host behaviors in a contamination-free environment, which was verified by culture-based methods.
  
  
  METHODS
  Open-field and marble-burying tests were used to analyze anxiety-like behaviors and locomotor activity in gnotobiotic BALB/c mice with a common genetic background in a sterile isolator. The monoamine levels in several regions of the brain were measured in germfree (GF) mice and commensal fecal microbiota-associated mice (EX-GF).
  
  
  RESULTS
  A 24-h exposure to the environment outside the sterile isolators rendered GF mice less anxious than those not contaminated, while there was no change in the locomotion. EX-GF mice, the gnotobiotic mice with normal specific pathogen-free microbiota, were less anxious and active than GF mice using open-field and marble-burying tests. The norepinephrine, dopamine, and serotonin turnover rates were higher in the EX-GF mice than in the GF mice in most regions of the brain, suggesting that monoaminergic neurotransmission might increase in the EX-GF mice comparing the GF mice. Monoassociation with Brautia coccoides reduced the anxiety level, but it did not affect the locomotor activity. In contrast, colonization with Bifidobacterium infantis decreased the locomotor activity, while having little effect on the anxiety level.
  
  
  CONCLUSIONS
  These results strongly support the current view that gut microorganisms modulate brain development and behavior.
authors.affiliation: Laboratory for Infectious Diseases, Isehara, Kanagawa, Japan. nishinoryo@tokai-u.jp
authors.forename: R
authors.initials: R
authors.lastname: Nishino
authors.forename: K
authors.initials: K
authors.lastname: Mikami
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Tomonaga
authors.forename: M
authors.initials: M
authors.lastname: Furuse
authors.forename: T
authors.initials: T
authors.lastname: Hiramoto
authors.forename: Y
authors.initials: Y
authors.lastname: Aiba
authors.forename: Y
authors.initials: Y
authors.lastname: Koga
authors.forename: N
authors.initials: N
authors.lastname: Sudo
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D001522:Behavior, Animal / Q000502:physiology*; D001644:Bifidobacterium; D001921:Brain / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D005106:Exploratory Behavior / Q000502:physiology*; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D005856:Germ-Free Life; D051379:Mice; D008807:Mice, Inbred BALB C; D064307:Microbiota; D009043:Motor Activity / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D013047:Specific Pathogen-Free Organisms
chemical_list: D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine