Dietary nucleotides influences intestinal barrier function, immune responses and microbiota in 3-day-old weaned piglets

Nucleotides (NTs) play a pivotal role in the growth and development of the intestine. This study aimed to evaluate the effects of nucleotides supplementation on the intestinal barrier function, immune responses and microbiota in 3-day-old weaned piglets. Ninety-six piglets weaned at 3-days after birth were randomly assigned to 2 treatments (6 replicates/treatment, 8 piglets/replicate) according to the average body weight. The dietary treatments consisted of the control (CON; fed a basal artificial milk) and nucleotides groups (NT; fed a basal artificial milk with 0.035 % nucleotides, the contents of CMP, UMP, AMP, GMP, and IMP were 1:1:1:1:1, respectively). Diarrhea rates were recorded, and blood and intestinal samples were collected on day 35 of the piglets. The current study showed that NTs supplementation tended to decrease the diarrhea rate of weaned piglets (P < 0.10). NTs increased villus height and the villus height-to-crypt depth (V/C) ratio in the ileum (P < 0.05). Dietary NTs up-regulated protein expression of ZO-1 in ileal mucosa (P < 0.05), and the protein expression of Occludin tended to increase. Furthermore, NTs up-regulated the mRNA expression of Mucin (MUC)2, while the mRNA expression of MUC4 was down-regulated in the ileal mucosa (P < 0.05). Besides, supplementation with NTs increased the ileal mucosa genes expression of IL-21, INF-gamma, IL-10, IL-4, IL-6 and TNF-alpha (P < 0.05). Furthermore, dietary NTs increased the protein expression of NF-kappa B, IL-6 and TNF-alpha (P < 0.05), and the proteins expression of Occludin and p-NF-kappa B tended to be up-regulated in the ileal mucosa (P < 0.10). Furthermore, NTs supplementation increased short chain fatty acid in the colonic (P < 0.05). And NTs supplementation reduced the Firmicutes/Bacteroidota ratio in the colon, at the genus level, NTs enriched the relative abundance of Prevotella, Faecalibacterium and Olsenella (P < 0.05). These data indicate that NTs could increase the villus height, increase the V/C, regulate the expression of tight junction protein and mucin, improve the intestinal barrier of piglets, regulate the secretion of cytokines, improve the biological immunity, increase the abundance of beneficial bacteria, and thus reduce the diarrhea of piglets.