Abstract

Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are characterized by chronic abdominal symptoms in the absence of an organic, metabolic or systemic cause that readily explains these complaints. Their pathophysiology is still not fully elucidated and animal models have been of great value to improve the understanding of the complex biological mechanisms. Over the last decades, many animal models have been developed to further unravel FGID pathophysiology and test drug efficacy. In the first part of this review, we focus on stress-related models, starting with the different perinatal stress models, including the stress of the dam, followed by a discussion on neonatal stress such as the maternal separation model. We also describe the most commonly used stress models in adult animals which brought valuable insights on the brain-gut axis in stress-related disorders. In the second part, we focus more on models studying peripheral, i.e., gastrointestinal, mechanisms, either induced by an infection or another inflammatory trigger. In this section, we also introduce more recent models developed around food-related metabolic disorders or food hypersensitivity and allergy. Finally, we introduce models mimicking FGID as a secondary effect of medical interventions and spontaneous models sharing characteristics of GI and anxiety-related disorders. The latter are powerful models for brain-gut axis dysfunction and bring new insights about FGID and their comorbidities such as anxiety and depression.

Highlights

  • Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent, occurring in 10–30% of the general population depending on the criteria used, and represent an important part of the workload of gastroenterology and primary care clinical practice

  • This protocol is mostly used as an acute stressor with a 1 to 2 h period of restraint. This short exposure already promoted [1] colonic hypersensitivity [134,135,136], [2] an increased influx of immune cells in the mucosa, mostly consisting of mast cells and eosinophils [135], [3] an intestinal hyperpermeability through the reorganization of the cytoskeleton in epithelial cells [134], [4] a delayed gastric emptying associated with the stress-induced sympathetic activation, increased corticotropin-releasing factor (CRF) [36, 137] and associated peptides [138] as well as active ghrelin concentration [137, 139, 140], and [5] changes in colonic morphology and a decrease of enteric glial cells especially in the submucosa plexus [135]. By using this model for 14 days, Yi et al could demonstrate the implication of the insular cortex in stress-induced visceral hypersensitivity, a region found to be abnormally activated in FGID patients [19] and more in general in patients with chronic pain [141]

  • Different infectious agents compared to humans; most models have used parasitic infections which is uncommon in human FGID The nutritional pattern differs between rodents and humans; evidence for immune reaction to food is still limited in human FGID Sensitivity to environmental factors which makes these model more difficult to reproduce Intervention is highly operator and experimental condition dependent

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Summary

INTRODUCTION

Functional gastrointestinal disorders (FGID), such as functional dyspepsia (FD) and irritable bowel syndrome (IBS) are highly prevalent, occurring in 10–30% of the general population depending on the criteria used, and represent an important part of the workload of gastroenterology and primary care clinical practice. This short exposure already promoted [1] colonic hypersensitivity [134,135,136], [2] an increased influx of immune cells in the mucosa, mostly consisting of mast cells and eosinophils [135], [3] an intestinal hyperpermeability through the reorganization of the cytoskeleton in epithelial cells [134], [4] a delayed gastric emptying associated with the stress-induced sympathetic activation, increased CRF [36, 137] and associated peptides [138] as well as active ghrelin concentration [137, 139, 140], and [5] changes in colonic morphology and a decrease of enteric glial cells especially in the submucosa plexus [135] By using this model for 14 days, Yi et al could demonstrate the implication of the insular cortex in stress-induced visceral hypersensitivity, a region found to be abnormally activated in FGID patients [19] and more in general in patients with chronic pain [141]. In a model of early weaning, the piglets are separated from their sow 1 week earlier

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