From intestinal permeability to dysmotility: The biobreeding rat as a model for functional gastrointestinal disorders

Tim Vanuytsel, Christophe Vanormelingen, Hanne Vanheel, Tatsuhiro Masaoka, Shadea Salim Rasoel, Joran Tóth, Els Houben, Kristin Verbeke, Gert De Hertogh, Pieter Vanden Berghe, Jan Tack, Ricard Farré

Research output: Contribution to journalArticlepeer-review

21 Citations (Scopus)


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.

Conclusion: 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.

Original languageEnglish
Article numbere111132
JournalPloS one
Issue number10
Publication statusPublished - 2014 Oct 29
Externally publishedYes

ASJC Scopus subject areas

  • General


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