Table 2.

The characteristics of in vitro, ex vivo, and in vivo intestine models.

Models	Types	Advantages	Limitations	References
In vitro-2D intestinal model	Caco-2 cells, IPEC-1 cells, IPEC-J2 cells, IPI-2I cells and PSI-1 cells, co-culture of different cell lines)	well-established and relatively cheap	only containing a single cell type without villus and crypt domain	[39,40,41,42,43,44]
In vitro-3D intestinal model	enteroids, also known as organoids or mini-guts	partially recapitulate the anatomy of native epithelium, have the ability to passage at an almost unlimited scale	the effects of substances on the luminal side are poorly investigated, considerable cost, do not contain the immune and stromal cells	[41,45,46,47,48,49]
Ex vivo	applied in humans, rodents, swine, poultry and horse	a more accurate model to mimic the physiology in vivo	fail to achieve long-term culture, careful and laborious preparation	[45,50,51]
In vivo	commonly used models include mouse, rat, chicken, turkey, fish, pig, sheep and bovine	provide the information based on the whole animals, thus they could corroborate the toxicity in humans effectively	the use of live animals should follow 3R (replacement, reduction and refinement) principle	[1]