Construction and Applications of Research Models for Intestinal Injury in Piglets: From In Vivo Models to In Vitro Models

During weaning, piglets are exposed to multiple nutritional, environmental, pathogenic, and psychological stressors and are therefore susceptible to structural and functional intestinal injury. The resulting damage can lead to diarrhea, impaired growth, and increased susceptibility to disease, seriously compromising piglet health and the efficiency of pig production. Establishing stable and reliable experimental models that match specific research objectives is essential for elucidating the mechanisms of intestinal injury in piglets and for evaluating nutritional interventions and prevention and control strategies. Current research on porcine intestinal injury uses a multilevel framework centered on porcine intestinal epithelial cells, porcine intestinal organoids, and in vivo piglet models. These models offer distinct advantages in experimental controllability, tissue-level physiological relevance, and whole-organism biological fidelity, respectively, while each has a defined scope of application. Focusing on intestinal injury in piglets, this review comprehensively summarizes the construction methods, injury-induction approaches, and evaluation systems used across these model levels and analyzes the key factors affecting model stability and the comparability of research findings. This review is intended to inform mechanistic studies of intestinal injury in piglets, model standardization, and the evaluation of nutritional intervention strategies. On this basis, the review concludes that porcine intestinal epithelial cell lines are most appropriate for high-throughput mechanistic screening, organoids for questions that require epithelial diversity and donor- or region-specific context, and in vivo piglet models for confirming physiological and production relevance. Because model reproducibility depends strongly on challenge dose, animal or donor age, culture conditions, and assessment endpoints, a coordinated sequence from cell lines to organoids and finally to in vivo validation should be combined with standardized reporting of model parameters.