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Postnatal nutrition restriction affects growth and immune response of intrauterine growth restricted piglets
Epidemiological studies and experimental models show that intrauterine growth restriction (IUGR) followed by accelerated postnatal growth is associated with increased susceptibility to diseases in later life. We hypothesized that postnatal nutrition restriction may improve intestinal development and immunity of IUGR neonates. Piglets with a birth weight near the mean litter birth weight (SD 0.5) were identified as NBW, whereas those with at least 1.5 SD lower birth weight were defined as IUGR. Twelve pairs of normal-birth weight (NBW) and IUGR piglets at 7 d of age were randomly assigned to adequate (ANI) or restricted nutrition intake (RNI) for a period of 21 days, which produced 4 experimental groups (birth weight/nutrition intake) as NBW-ANI, IUGR-ANI, NBW-RNI and IUGR-RNI (n=6 per group). The NBW-ANI and IUGR-ANI piglets had free access to formula milk, while the NBW-RNI piglets had same intake of formula milk as IUGR-ANI piglets. In order to achieve the same degree of nutrition restriction as NBW piglets, the formula milk intake of IUGR-RNI piglets was based on the calculation that the formula milk intake of IUGR-ANI piglets multiplied by the formula milk intake of NBW-RNI piglets and divided by the formula intake of NBW-ANI piglets. At d 28, blood and intestinal samples were collected at necropsy and analyzed for cellular immune response and expression of innate immunity and DNA methylation-related genes. Data were analyzed by SPSS software using the MIXED procedure. The results indicated that both IUGR and postnatal nutrition restriction decreased (-26%, P=0.002) ADG during the experimental period, but there was comparable ADG between IUGR-ANI and NBW-RNI piglets. The relative weight of intestine, heart or brain to body weight was higher (+9%, P=0.091; +23%, P=0.025 and +41%, P=0.001; respectively) in IUGR than that in NBW piglets. Irrespective of body weight, number of peripheral leucocytes, lymphocytes and monocytes were significantly decreased (-25%, P=0.006; -37%, P=0.001 and -82%, P=0.009; respectively) by RNI, whereas the ratio of CD4+ to CD8+ in blood was significantly increased (+27%, P=0.034) by RNI, however, it did not markedly differ between NBW-ANI and IUGR-RNI piglets. Likewise, ileal mRNA expression of innate immunity and DNA methylation-related genes (TLR-9 and DNMT1) were up-regulated in piglets with RNI (+31%, P=0.004 and +57%, P=0.001; respectively), particularly increased in IUGR-RNI relative to IUGR-ANI piglets. In conclusion, the present study indicated that postnatal nutrition restriction may affect systematic and intestinal immune response of IUGR piglets.
Keywords: pigs, intestine, innate immunity