The Weaning of Pigs: Mechanistic Outcomes to Intestinal Immunity and Integrity.

Weaning is a critical stage in pigs characterized by abrupt maternal separation, dietary transition, social mixing, relocation, and increased exposure to environmental and pathogenic challenges. These stressors occur during a period of physiological immaturity and collectively disrupt intestinal homeostasis. Dysbiosis alters luminal signaling and microbial metabolite profiles, contributing to activation of innate immune pathways, oxidative imbalance, increased intestinal permeability, and impaired capacity for epithelial maintenance, ultimately compromising nutrient absorption and growth performance. Despite their diverse origins, these stressors converge on shared biological pathways, including pattern-recognition receptor activation, cytokine amplification, redox imbalance, and tight junction disruption, which sustain mucosal inflammation and barrier dysfunction during the post-weaning period. This review combines the current understanding of how weaning-associated and dietary stressors, including dietary antigens, non-starch polysaccharides, enteric pathogens, and mycotoxins, affect intestinal immunity and epithelial integrity in pigs. Nutritional interventions are evaluated based on their ability to influence common epithelial-immune pathways. Functional feed additives can regulate host-microbe interactions, dampen inflammatory signaling, enhance redox homeostasis, and maintain epithelial integrity. Overall, post-weaning intestinal dysfunction should be considered a multifactorial condition driven by interconnected stress pathways, and nutritional approaches targeting these shared mechanisms may enhance intestinal function and growth performance in weaned pigs.