CN
1. Preface
Intrauterine growth restriction (IUGR) is a serious problem in human infants and animals. Pigs are multi-litters and have severe IUGR. IUGR significantly affects neonatal survival, postnatal growth, immunity, and lifelong health in animals. While better management techniques and mammalian nutrient regulation have contributed significantly to ameliorating complications, IUGR remains an important issue because understanding of the effects of nutrition on neonatal growth regulation mechanisms is still inadequate. IUGR can significantly affect neonatal intestinal development and intestinal barrier function, and can cause long-term growth disorders. Studying the effects of new nutrients on IUGR may help address complications associated with IUGR.
Tributyrin (TB) is a glyceride containing 3 butyric acids that can be used as a probutyric drug. Butyric acid is a short-chain fatty acid (SCFA) that protects the intestine by inhibiting bacterial growth, increasing mucosal cell proliferation, and promoting intestinal cell development and colon defense function. Butyric acid also has immune and anti-inflammatory effects. In addition, adding sodium butyrate before weaning is more effective in promoting feed intake and body growth than adding sodium butyrate after weaning. A study of weaned piglets showed that the addition of sodium butyrate only improved the piglets' initial adaptation to solid foods. Another study on weaned piglets also showed that adding sodium butyrate to feed does not promote body growth, but may regulate their immunity. The use of TB can reduce the shortcomings of butyric acid; TB is better tolerated orally than butyrate and has been used as a food additive. The role of TB in Suckling piglets is unclear, and the effects of TB on IUGR in humans and livestock have not been studied. The aim of this study was to investigate the effects of TB supplementation during lactation on growth, intestinal digestion and barrier function of IUGR newborn piglets.
2. Summary
Background & Objective: Growth restriction in newborns with intrauterine growth restriction (IUGR). Tributyrate (TB), a prodrug of butyric acid, promotes growth in animals. The aim of this study was to investigate the effects of TB supplementation on the growth of newborn piglets with IUGR. Methods: Sixteen IUGR and eight NBW(normal weight) newborn piglets were weaned on day 7 and fed either basic artificial milk (NBW and IUGR group) or basic artificial milk +0.1% TB-supplemented artificial milk (IT group, IUGR piglets fed TB-supplemented artificial milk) until day 21 (n=8). Body weight was measured at days 0,7, 10, 14, 17 and 20. The digestive enzyme activity, intestinal morphology, immunoglobulin level and gene expression of IgG, FcRn and GPR41 in small intestine were analyzed. Results: The weight of piglets in IUGR group and IT group was similar, and the weight of piglets in IUGR group was lower than that in NBW group on day 10 and 14. However, on day 17, the weight of the IT group improved compared with the IUGR group (P < 0.05). The piglets were killed on day 21. Compared with NBW piglets,IUGR piglets had impaired development of immune organs and small intestine, impaired intestinal villi morphology, decreased activity of most intestinal digestive enzymes (P < 0.05), decreased sIgA and immunoglobulin levels in ileum (P < 0.05), and down-regulated expression of intestinal immunoglobulin and GPR41 (P < 0.05). Compared with IUGR group, the development of spleen and small intestine of piglets in IT group was better (P < 0.05), intestinal villi morphology was improved, intestinal villi surface area was increased (P < 0.05), digestive enzyme activity was increased (P < 0.05), and immunoglobulin and GPR41 mRNA expression were up-regulated (P < 0.05). Conclusion: TB supplementation during lactation can improve the growth and development, intestinal digestion and barrier function of IUGR piglets.
Keywords: tributyrin, IUGR, lactation stage, small intestine, piglet
3. Test results
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Figure 1 Weight changes of IUGR piglets supplemented with TB during lactation. Eight litters of newborn piglets were selected. Two IUGR piglets and one normal weight piglet were selected for each litter. Piglets in NBW group and IUGR group were fed basic artificial milk, respectively, while piglets in IT group (IUGR group +TB) were fed basic artificial milk +0.1%TB from 7 to 21 days. Data are expressed as mean ±SEM, n=8. There was no significant interaction between treatment group and age (P > 0.05). The difference between groups was statistically significant (P < 0.001). Among the three groups, the weight of piglets in NBW group was the highest, followed by that in IT group, and the lowest in IUGR group (P < 0.01). The daily treatment effect was significant (P < 0.001). Weight of all piglets increased with age (data not shown). The average body weight of piglets in IUGR group and IT group at day 0, 7, 11 and 14 was lower than that in NBW group (P < 0.05). However, on days 17 and 20, the body weight of piglets in IT group was improved compared with that in IUGR group (P < 0.05), and the body weight of piglets in IT group was close to that in NBW group (P > 0.05)(FIG. 1).
Table 3 Effects of TB supplementation during lactation on small intestine and immune organ development of IUGR piglets
Figure 2 Intestinal villus morphology of piglets in NBW, IUGR and IT groups
Table 4 Effects of TB supplementation during lactation on SI villus morphology of IUGR piglets
Table 5 Effects of TB supplementation during lactation on SI digestive enzyme activity in IUGR piglets.
Table 6 Effects of TB supplementation on SI mucosal immunoglobulin levels in IUGR piglets during lactation
Table 7 Effects of TB supplementation during lactation on the relative gene expression of small intestinal IgG and its receptor GPR41 in IUGR piglets
Experimental conclusion
In conclusion, the supplementation of triglyceride during breastfeeding can promote the body weight gain of IUGR piglets, improve the development of immune organs and small intestine, improve the intestinal villi morphology, increase the intestinal villi surface area and intestinal digestive enzyme activity, increase mucosal immunoglobulin level, and up-regulate the differential gene expression of IgG and GPR41 in ileum. Since the intestinal structure and physiology of humans and pigs are very similar, IUGR newborn piglets can also serve as a good model for studying intestinal structure and function in humans. Our study has identified a new way to treat IUGR shortly after birth by supplementing the diet with tributyrin during lactation. However, more research is needed if we need to apply it to human clinical nutrition.
