Table 2.

Strengths and limitations for common models of Functional GI disorders.

Model	Strengths	Limitations	Part of the GI tract studied
Pre-natal stress	Allows to study epigenetic changes	Individual variation among animals, around 80 to 95% of animals are sensitized by the stress applied	Small bowel and colon
Maternal separation	Reproduces maternal neglect and mistreatment of FGID patients		Colon
Limited bedding	Non-interventional model, avoids experimenter influence		Colon
Odor shock conditioning	Specifically mimics alterations in learning and fear conditioning		colon
Water avoidance	Strong acute models reproducing a strong stressor and mimicking resilience in an uncomfortable situation	Limited construct validity: physical constraint is not a factor commonly encountered in the etiology of FGID in patients	Stomach Ileum (more affected) colon
Partial restraint stress			Stomach and colon
Crowding stress	Models capture the social component in stress-induced FGID	Social organization, and individual reactions to stress are obviously less standardized and more complicated in humans	Small intestine and colon
Social isolation			Colon
Combined stress	Good model to reproduce anetiology commonly found in human	Because of the more complex interaction of stressors and depending on the protocol used, results tend to be more difficult to reproduce	Colon
Post-inflammatory	Reproduces low-grade inflammation often found in FGID e.g., after infection or in IBD in remission	Limited construct validity: interventional models using irritants/chemicals	Local effect depending on the targeted organ: mainly Stomach and colon
Post-infectious	Model for post-infectious FGID which allow a detailed study of dysbiosis involved in FGID	Different infectious agents compared to humans; most models have used parasitic infections which is uncommon in human FGID	Depending on the infection, small bowel or colon
Food allergy	Murine immune response in case of loss of oral tolerance closely resembles the human counterpart	The nutritional pattern differs between rodents and humans; evidence for immune reaction to food is still limited in human FGID	Colon
Spontaneous models	Non-interventional models, good face and construct validity	Sensitivity to environmental factors (food, stressors…) which makes these model more difficult to reproduce	Stomach, small bowel, colon
Postoperative Ileus	Good construct validity. Allows to study of the mechanisms of interventional surgery as a trigger of intestinal alterations	Intervention is highly operator and experimental condition dependent	Small bowel
Manipulation central nervous system	Suitable for mechanistic studies of the involvement of the central nervous system	Limited construct validity: far from human etiology	Mainly colon
Genetic model	Ideal models to study a specific genetic target and its role in FGID	Compensation phenomena; human FGID is not monogenetic	If KO: all levels of the GI tract If conditional KO: organ targeted
Cross sensitization	Understanding of the overlap in neuronal pathways which is common in human FGID	Interventional models using irritants	Depending on the organs targeted (mainly bladder and colon)

KO, knockout; FGID, functional gastrointestinal disorders; IBD, inflammatory bowel disease.