title: Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.
abstract: BACKGROUND
  There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice.
  
  
  METHODS
  Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood.
  
  
  RESULTS
  Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain.
  
  
  CONCLUSIONS
  Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition.
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland. Electronic address: Lieve.Desbonnet@glasgow.ac.uk.
authors: Lieve
authors: L
authors: Desbonnet
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Psychiatry, University College Cork, Cork, Ireland.
authors: Gerard
authors: G
authors: Clarke
authors: School of Medicine, University College Cork, Cork, Ireland.
authors: Alexander
authors: A
authors: Traplin
authors: Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors: Orla
authors: O
authors: O'Sullivan
authors: Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors: Fiona
authors: F
authors: Crispie
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors: Rachel D
authors: RD
authors: Moloney
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Teagasc Food Research Centre, Moorepark, Fermoy, Cork, Ireland.
authors: Paul D
authors: PD
authors: Cotter
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Psychiatry, University College Cork, Cork, Ireland.
authors: Timothy G
authors: TG
authors: Dinan
authors: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland; Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.
authors: John F
authors: JF
authors: Cryan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000187:drug effects / Q000502:physiology*; D041981:Gastrointestinal Tract / Q000382:microbiology*; D051379:Mice; D014364:Tryptophan / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D019208:Brain-Derived Neurotrophic Factor; D014364:Tryptophan
keywords: Adolescence; Antibiotics; Anxiety; BDNF; Cognition; Gut microbiota; Vasopressin