title: Altered colonic function and microbiota profile in a mouse model of chronic depression.
abstract: BACKGROUND
  Depression often coexists with the irritable bowel syndrome (IBS) which is characterized by alterations in gut function. There is emerging evidence that the microbial composition (microbiota) of the gut is altered in IBS, but the basis for this is poorly understood. The aim of this study was to determine whether the induction of chronic depression results in changes in the colonic function and in its microbial community, and to explore underlying mechanisms.
  
  
  METHODS
  Bilateral olfactory bulbectomy (OBx) was used to induce depression-like behavior in mice. Colonic function was assessed by measuring muscle contractility, pellet excretion, c-fos activity, and serotonin levels. Microbiota profiles were obtained using denaturing gradient gel electrophoresis (DGGE). The hypothalamic-pituitary axis (HPA) was assessed by the hypothalamic expression of corticotropin-releasing hormone (CRH). In separate studies, mice without OBx received CRH via intracerebroventricular (ICV) infusion for 4 weeks prior to assessing colonic function and microbiota profiles.
  
  
  RESULTS
  Olfactory bulbectomy mice demonstrated chronic depression- and anxiety-like behaviors associated with elevated central CRH expression and increases in c-Fos activity, serotonin levels, and motility in the colon. These changes were accompanied by an altered intestinal microbial profile. Central CRH administration produced similar changes in behavior and motility and altered the microbiota profile in the colon.
  
  
  CONCLUSIONS
  The induction of chronic depression alters motor activity and the microbial profile in the colon likely via activation of the HPA. These findings provide a basis for linking the behavioral and gastrointestinal manifestations of IBS.
authors.affiliation: Department of Medicine, Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada.
authors.forename: A J
authors.initials: AJ
authors.lastname: Park
authors.forename: J
authors.initials: J
authors.lastname: Collins
authors.forename: P A
authors.initials: PA
authors.lastname: Blennerhassett
authors.forename: J E
authors.initials: JE
authors.lastname: Ghia
authors.forename: E F
authors.initials: EF
authors.lastname: Verdu
authors.forename: P
authors.initials: P
authors.lastname: Bercik
authors.forename: S M
authors.initials: SM
authors.lastname: Collins
mesh_terms: D000818:Animals; D003106:Colon / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D003863:Depression / Q000378:metabolism / Q000382:microbiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000503:physiopathology*; D060888:Real-Time Polymerase Chain Reaction; D012701:Serotonin / Q000378:metabolism
chemical_list: D012701:Serotonin; D003346:Corticotropin-Releasing Hormone
keywords: CRH; IBS; colonic motility; depression; microbiome