| Ultra-early weaning has been shown to have a positive effect on improving the survival rate of suckling piglets and the productivity of sows,as well as reducing the risk of disease transmission.However,ultra-early weaning could also lead to problems such as damage to the intestinal mucosal barrier and microbial dysbiosis,resulting in increased piglet diarrhea and growth retardation.Nucleotides,as important small-molecule compounds in the body,play an important role in regulating the growth and development of young animals and intestinal health,especially during special periods such as rapid animal growth,immunosuppression,or limited nutrient intake.This study aims to investigate the effects and mechanism of dietary with nucleotides on nucleotide metabolism and intestinal barrier function of early weaned piglets.The main results of the study are as follows:1 、 Effects of dietary nucleotides on growth performance,serum biochemistry,and nucleotide metabolism of ultra-early weaned pigletsIn this study,a total of 96 3d weaned piglets(2.3 ± 0.002 kg)were randomly assigned into two treatment groups(6 replicates per group,8 piglets per replicates).The control group was fed with basic breast milk,the nucleotides group was fed with basic breast milk supplemented with 0.035%nucleotides,including AMP,UMP,CMP,GMP,and IMP.The experimental period was 32 days.Results showed that compared with the control group,nucleotides supplementation had no significant effect on final weight and average daily gain of ultra-early weaned piglets(P > 0.10),but tended to reduce the total diarrhea rate(P = 0.093)and significantly decrease the diarrhea rate at 12 days of age(P < 0.05).Additionally,compared with the control group,dietary nucleotides decreased serum levels of low-density lipoprotein cholesterol(LDL-C),total bile acid(TBA),and the ratio of lowdensity lipoprotein cholesterol to total cholesterol(LDL-C/CHOL)in weaned piglets(P < 0.05).Further research on the nucleotide metabolism levels of weaned piglets revealed that dietary nucleotides reduced contents of uridine and uridine monophosphate in serum,increased levels of uracil and uridine monophosphate in the liver of piglets(P < 0.05).and upregulated the m RNA expression of SLC28A3 in the duodenum and jejunum mucosa(P < 0.05).Interestingly,nucleotides down-regulated multienzyme complex(CAD)m RNA expression and uridine monophosphate synthetase(UMPS)enzyme activity in liver(P < 0.05).Therefore,nucleotides could alleviate diarrhea and regulate the biochemical indices related to lipid metabolism and nucleotide metabolism in ultra-early weaned piglets.2、Effects of dietary nucleotides on intestinal physical,chemical,and immune barrier functions of ultra-early weaned pigletsThe results showed that compared with the control group,dietary nucleotides increased the ileal villus height and villus/crypt ratio,up-regulated the expression of ZO-1 m RNA,reduced the expression of Claudin-1 m RNA in the jejunum mucosa of weaned piglets(P < 0.05),and increased the expression of ZO-1 protein in the ileum mucosa(P < 0.05).In addition,nucleotides upregulated the expression of MUC2 m RNA,and downregulated the expression of MUC4 m RNA in the piglet ileum mucosa(P < 0.05).Moreover,nucleotides increased the expression of IL-21,IL-10 and INF-γ m RNA in the duodenum mucosa(P < 0.05);increased the expression of INF-γ,IL-4 and IL-1β m RNA in the jejunum mucosa,while decreased the expression of IL-12 and TNF-αm RNA(P < 0.05);increased the expression of IL-21,INF-γ,IL-10,IL-4,IL-6and TNF-α m RNA in the ileum mucosa(P < 0.05).Furthermore,nucleotides increased the expression of IL-6,TNF-α and NF-κB protein in the ileum mucosa(P < 0.05).In conclusion,nucleotides may improve the intestinal barrier function of ultra-early weaned piglets by improving the morphology of small intestinal villi,regulating the expression of tight junction proteins and mucins,and regulating the expression of key proteins in the NF-κB signaling pathway to regulate cytokine secretion.3、Effects of dietary nucleotides on the gut microbial barrier function of ultra-early weaned pigletsThe results showed that compared with the control group,dietary nucleotides affected the beta diversity of colonic bacteria in ultra-early weaned piglets.At the phylum level,nucleotides significantly reduced the abundance of unclassified＿k＿＿norank＿d＿＿Bacteria,Campilobacterota and the Firmicutes/Bacteroidota ratio in the colonic microbiota of weaned piglets(P <0.05).At the genus level,nucleotides increased the relative abundance of Blautia,Faecalibacterium and Prevotella,while decreased the relative abundance of Clostridium＿sensu＿stricto＿1 and Terrispobacter(P < 0.05).In addition,nucleotides significantly increased the content of acetic acid,isobutyric acid,isovaleric acid and valeric acid in the colonic contents(P <0.05).In conclusion,nucleotides may enhance the intestinal microbial barrier function of piglets by regulating the microbiota structure and short-chain fatty acid composition in weaned piglets.In summary,dietary with nucleotides may improve the physical barrier,chemical barrier,immune barrier and microbial barrier function of the intestinal tract of ultra-early piglets by affecting the nucleotide metabolism,alleviating the diarrhea caused by early weaning of piglets,and providing a theoretical basis for nucleotides as a nutritional feed additive for regulating pig intestinal health. |
