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Simple Summary  The gut mucosa of pigs, which contains intestinal epithelium and subepithelial immune cells, forms a barrier against microorganisms. Nonetheless, infectious diseases of the digestive tract remain the most frequent and recurrent conditions in the swine industry. Changes in intestinal morphology and structure primarily occur at birth and during weaning. However, the difference in the intestinal structures between neonatal and weaned piglets remains unclear. In this study, for the first time, we evaluated the differences in the small intestine between neonatal (0-day-old) and weaned piglets (21-day-old) and analyzed the morphology and immunological components of the small intestines of 0- and 21-day-old piglets, thereby providing preliminary data for future mechanistic studies.    Abstract  The gut is one of the body’s major immune structures, and the gut mucosa, which contains intestinal epithelium and subepithelial immune cells, is the primary site for eliciting local immune responses to foreign antigens. Intestinal immune system development in pigs is a transitional period during birth and weaning. This study compares the morphological and immunological differences in the small intestine of neonatal and weaned piglets to potentially prevent intestinal infectious diseases in neonatal piglets. Histological analyses of weaned piglet intestines showed increased crypt depth, higher IEL count, and larger ileal Peyer’s patches compared with those of neonates. Additionally, the ileal villi of weaned piglets were longer than those of neonatal piglets, and claudin-3 protein expression was significantly higher in weaned than in neonatal piglets. The numbers of CD3 +  T, goblet, and secretory cells were also higher in the small intestines of weaned piglets than in those of neonates. No significant differences were observed in the secretory IgA-positive cell number in the jejunum of weaned and neonatal piglets. The mRNA expression of most pattern recognition receptors genes in the duodenum and jejunum was higher in the weaned than neonatal piglets; however, the opposite was true in the ileum. The mRNA levels of IL-1β and TNF-α in the jejunal and ileal mucosa were higher in weaned piglets than in neonatal piglets. There were significantly fewer CD3 + , CD4 + , and CD8 +  T cells from peripheral blood-mononuclear cells in neonatal piglets. Our study provides insights regarding the different immune mechanisms within the small intestines of 0- and 21-day-old piglets. Studies on the additional developmental stages and how differences in the small intestines affect the response of pigs to pathogens remain warranted.

Single-Blinded Study Highlighting the Differences between the Small Intestines of Neonatal and Weaned Piglets