title: The anxiolytic effect of Bifidobacterium longum NCC3001 involves vagal pathways for gut-brain communication.
abstract: BACKGROUND
  The probiotic Bifidobacterium longum NCC3001 normalizes anxiety-like behavior and hippocampal brain derived neurotrophic factor (BDNF) in mice with infectious colitis. Using a model of chemical colitis we test whether the anxiolytic effect of B. longum involves vagal integrity, and changes in neural cell function. Methods  Mice received dextran sodium sulfate (DSS, 3%) in drinking water during three 1-week cycles. Bifidobacterium longum or placebo were gavaged daily during the last cycle. Some mice underwent subdiaphragmatic vagotomy. Behavior was assessed by step-down test, inflammation by myeloperoxidase (MPO) activity and histology. BDNF mRNA was measured in neuroblastoma SH-SY5Y cells after incubation with sera from B. longum- or placebo-treated mice. The effect of B. longum on myenteric neuron excitability was measured using intracellular microelectrodes.
  
  
  RESULTS
  Chronic colitis was associated with anxiety-like behavior, which was absent in previously vagotomized mice. B. longum normalized behavior but had no effect on MPO activity or histological scores. Its anxiolytic effect was absent in mice with established anxiety that were vagotomized before the third DSS cycle. B. longum metabolites did not affect BDNF mRNA expression in SH-SY5Y cells but decreased excitability of enteric neurons.
  
  
  CONCLUSIONS
  In this colitis model, anxiety-like behavior is vagally mediated. The anxiolytic effect of B. longum requires vagal integrity but does not involve gut immuno-modulation or production of BDNF by neuronal cells. As B. longum decreases excitability of enteric neurons, it may signal to the central nervous system by activating vagal pathways at the level of the enteric nervous system.
authors: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, ON, Canada.
authors: P
authors: P
authors: Bercik
authors: A J
authors: AJ
authors: Park
authors: D
authors: D
authors: Sinclair
authors: A
authors: A
authors: Khoshdel
authors: J
authors: J
authors: Lu
authors: X
authors: X
authors: Huang
authors: Y
authors: Y
authors: Deng
authors: P A
authors: PA
authors: Blennerhassett
authors: M
authors: M
authors: Fahnestock
authors: D
authors: D
authors: Moine
authors: B
authors: B
authors: Berger
authors: J D
authors: JD
authors: Huizinga
authors: W
authors: W
authors: Kunze
authors: P G
authors: PG
authors: McLean
authors: G E
authors: GE
authors: Bergonzelli
authors: S M
authors: SM
authors: Collins
authors: E F
authors: EF
authors: Verdu
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001644:Bifidobacterium / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D016264:Dextran Sulfate / Q000494:pharmacology; D017615:Enteric Nervous System / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005243:Feces / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000294:innervation / Q000382:microbiology; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D010919:Placebos; D019936:Probiotics / Q000494:pharmacology / Q000627:therapeutic use; D014628:Vagotomy; D014630:Vagus Nerve / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D019208:Brain-Derived Neurotrophic Factor; D010919:Placebos; D016264:Dextran Sulfate