Table 4.

A comparative overview of the advantages, disadvantages, and applications of experimental models for the study of NEC

Model Organism	Advantages	Disadvantages	Applications
Rats	Low cost.	Lack of readily available transgenic strains.	Biomarker identification.
	High litter size.	Marked difference in bacterial/endotoxin tolerance between rats and human (increased tolerance in rats).	Investigation of pathogenesis and disease mechanisms.
	Ready availability.	Uncertain relevance to human disease.	Drug discovery.
	Ease of disease induction.
	Uniform genetic backgrounds.
	Short gestational period.
Mice	Low cost.	Difficulty in feeding and handling small and fragile pups.	Biomarker identification.
	High litter size.		Investigation of pathogenesis and disease mechanisms.
	Ready availability.
	Ease of disease induction.		Drug discovery.
	Uniform genetic backgrounds.
	Short gestational period.
	High genetic similarity.
	Availability of knockout strains.
	Sophisticated transgenic approaches.
Piglets	High degree of anatomic, developmental, nutritional, functional and physiological similarity of the gastrointestinal tract with human infants.	High cost.	Drug discovery.
	Similar size to human preterm infants.	Difficulty in maintaining and feeding a group of premature piglets.	Validation of biochemical pathways.
		Variability of genetic background.	Study of pathogenesis.
		Need for a well-equipped surgical facility to perform cesarean section and safely manage a litter of piglets.	Evaluation of specific feeding regimens.
			Preclinical drug studies.
			Development of early noninvasive spectroscopic diagnostic methods.
Hamsters and rabbits	Relatively large size.	High cost relative to rats and mice.	Underlying mechanisms of disease.
	Ease of handling.	Variability of genetic background.
Nematode (Caenorhabditis elegans)	Relatively low cost.	Lacks many physiological and dietary features of mammals, making the clinical and scientific relevance to NEC uncertain.	The study of single cells and cell-microbial interactions.
	Easy genetic manipulation.
	Well-characterized genome.
	Epithelialized gastrointestinal tract.
Invertebrate (Drosophila)	Low cost.	Relevance to disease in mammalian systems is uncertain.	Study of underlying mechanisms.
	Easy genetic manipulation.