Abstract
The current study aimed to determine whether dietary nucleotides supplementation could improve growth performance, intestinal development and immune function of intra-uterine growth restricted (IUGR) neonate using pig as animal model. A total of 14 pairs of normal birth weight (NBW) and IUGR piglets (7 days old) were randomly assigned to receive a milk-based control diet (CON diet) or diet supplemented with nucleotides (NT diet) for a period of 21 days. Blood samples, intestinal tissues and digesta were collected at necropsy and analyzed for morphology, digestive enzyme activities, microbial populations, peripheral immune cells, expression of intestinal innate immunity and barrier-related genes and proteins. Compared with NBW piglets, IUGR piglets had significantly lower average daily dry matter intake and body weight gain (P<0.05). Moreover, IUGR markedly decreased the villous height and villi: crypt ratio in duodenum (P<0.05), as well as the maltase activity in jejunum (P<0.05). In addition, IUGR significantly decreased the serum concentrations of IgA, IL-1βand IL-10 (P<0.05), as well as the percentage of peripheral lymphocytes (P<0.05). Meanwhile, the down-regulation of innate immunity-related genes such as TOLLIP (P<0.05), TLR-9 (P = 0.08) and TLR-2 (P = 0.07) was observed in the ileum of IUGR relative to NBW piglets. Regardless of birth weight, however, feeding NT diet markedly decreased (P<0.05) feed conversion ratio, increased the villous height in duodenum (P<0.05), activities of lactase and maltase in jejunum (P<0.05), count of peripheral leukocytes (P<0.05), serum concentrations of IgA and IL-1β as well as gene expressions of TLR-9, TLR-4 and TOLLIP in ileum (P<0.05). In addition, expressions of tight junction proteins (Claudin-1 and ZO-1) in ileum were markedly increased by feeding NT diet relative to CON diet (P<0.05). These results indicated that IUGR impaired growth performance, intestinal and immune function, but dietary nucleotides supplementation improved nutrients utilization, intestinal function and immunity.
Highlights
Intra-uterine growth restriction (IUGR) refers to the impaired growth and development of a mammalian embryo/fetus or its organs during pregnancy [1, 2]
Studies have shown that functions of internal organs, nutrient metabolism and immune system are impaired in IUGR human-beings [5,6,7,8] and animal models [9,10,11]
Regardless of body weight (BW), average daily gain (ADG) tended to be higher in piglets receiving nucleotides-supplemented diet (NT) relative to control diet (CON) diet, feed conversion ratio (FCR) was markedly decreased (−17%, P
Summary
Intra-uterine growth restriction (IUGR) refers to the impaired growth and development of a mammalian embryo/fetus or its organs during pregnancy [1, 2]. Studies have shown that functions of internal organs, nutrient metabolism and immune system are impaired in IUGR human-beings [5,6,7,8] and animal models [9,10,11]. The milk of mammal animals have higher contents than any other food origin [16] Under certain conditions such as stress, immunological challenges and disease state, exogenous nucleotides become essential nutrients to optimize intestinal and immunological function [15, 17, 18]. This study was to determine whether dietary supplementation of nucleotides could improve the growth performance, intestinal development and immune function of IUGR neonates. As a multi-fetal domestic animal, pigs have exhibited naturally occurred IUGR due to utero-placental insufficiency [23]
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