title: From intestinal permeability to dysmotility: the biobreeding rat as a model for functional gastrointestinal disorders.
abstract: BACKGROUND
  Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) rat.
  
  
  METHODS
  Normoglycemic BB-diabetes prone (DP) and control rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function.
  
  
  RESULTS
  Both structural and functional evidence of increased intestinal permeability was found in young BB-DP rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstrated.
  
  
  CONCLUSIONS
  In the BB-rat, mucosal inflammatory cell infiltration is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Tim
authors.initials: T
authors.lastname: Vanuytsel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Christophe
authors.initials: C
authors.lastname: Vanormelingen
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Hanne
authors.initials: H
authors.lastname: Vanheel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Masaoka
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Shadea
authors.initials: S
authors.lastname: Salim Rasoel
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Joran
authors.initials: J
authors.lastname: Tóth
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Els
authors.initials: E
authors.lastname: Houben
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Kristin
authors.initials: K
authors.lastname: Verbeke
authors.affiliation: Department of Pathology, University Hospital, University of Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: De Hertogh
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Vanden Berghe
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Jan
authors.initials: J
authors.lastname: Tack
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos II, Barcelona, Spain.
authors.forename: Ricard
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000378:metabolism* / Q000503:physiopathology; D005769:Gastrointestinal Motility; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000254:growth & development / Q000294:innervation / Q000378:metabolism; D009197:Myenteric Plexus / Q000254:growth & development / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB