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. 2016 Jun 15;11(6):e0157314.
doi: 10.1371/journal.pone.0157314. eCollection 2016.

Dietary Nucleotides Supplementation Improves the Intestinal Development and Immune Function of Neonates with Intra-Uterine Growth Restriction in a Pig Model

Lianqiang Che  1 , Liang Hu  1 , Yan Liu  1 , Chuan Yan  1 , Xie Peng  1 , Qin Xu  1 , Ru Wang  1 , Yuanfang Cheng  1   2 , Hong Chen  3 , Zhengfeng Fang  1 , Yan Lin  1 , Shengyu Xu  1 , Bin Feng  1 , Daiwen Chen  1 , De Wu  1
Affiliations

Dietary Nucleotides Supplementation Improves the Intestinal Development and Immune Function of Neonates with Intra-Uterine Growth Restriction in a Pig Model

Lianqiang Che et al. PLoS One. .

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.

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Conflict of interest statement

Competing Interests: The support of Tongwei group Co., Ltd., does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Effect of dietary nucleotides supplementation on the plasma concentration of D-xylose of IUGR and NBW piglets.
Values are means, with standard errors represented by vertical bars, n = 7 in each group. IUGR, intrauterine growth restriction; NBW, normal-birth weight; CON, control diet; NT, nucleotides-supplemented diet; ZO-1, zonula occludens protein-1; a,b Mean values with unlike letters were significantly different (P< 0.05). * P< 0.05 for the respective sources of variation.
Fig 2
Fig 2. Effects of dietary nucleotides supplementation on protein expressions of Claudin-1 and ZO-1 in the ileum of IUGR and NBW piglets.
Values are means, with standard errors represented by vertical bars, n = 7 in each group. The value of protein expression means densitometry units of selected protein/densitometry units of β-actin detected by Western blotting. IUGR, intrauterine growth restriction; NBW, normal-birth weight; CON, control diet; NT, nucleotides-supplemented diet; ZO-1, zonula occludens protein-1. a,bMean values with unlike letters were significantly different (P< 0.05).
See this image and copyright information in PMC

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