The factors that cause post-natal growth retardation (PGR) in pigs are complicated; however, metabolic and immune system impairment seem to be involved. The purpose of this study was to investigate the changes of blood parameters, hormone profiles, antioxidant capacity, and immune responses in PGR pigs. Blood and small intestinal mucosa samples were collected from 42-days-old PGR and healthy pigs. The results showed that compared with the healthy group, the relative weight of spleen and kidney were greater, but the liver was lighter in PGR pigs (P < 0.05). The PGR pigs had increased serum alanine transaminase, urea nitrogen, blood ammonia, IgG, and complement 4, but decreased glucose and albumin (P < 0.05). The higher levels of serum leptin (LEP) and thyroxin (T4), and the lower levels of insulin-like growth factor-1 (IGF-1), 5-hydroxytryptamine (5-HT), somatostatin (SS), and agouti gene-related protein (AgRP) were observed in PGR pigs (P < 0.05). Consistent with the serum levels of hormones, the mRNA levels of gut hormones and their receptors were also altered in intestinal mucosa from PGR pigs (P < 0.05). The PGR pigs exhibited higher plasma concentrations of interleukin-1β (IL-1β), IL-6, IL-8, and transformed growth factor beta (TGFβ) (P < 0.05). However, the mRNA expressions of several cytokines were lower in the small intestinal mucosa of PGR pigs (P < 0.05). Abnormal antioxidant indexes in serum of PGR pigs were observed, which was in accordance with the reduced mRNA expression of several anti-oxidative genes in the small intestinal mucosa of PGR pigs (P < 0.05). These data demonstrate that an abnormal gut hormone system, immune dysfunction, and decreased antioxidant capacity may contribute to PGR in pigs. These changes could provide a valuable target in the regulation of post-natal growth retardation in animals and humans.

Postnatal growth retardation (PGR) is common in piglets. Abnormal development in small intestine was casually implicated in impaired growth, but the exact mechanism is still implausible. The present study unveiled transcriptome profile of jejunal mucosa, the major site of nutrient absorption, in PGR and healthy piglets using RNA-sequencing (RNA-seq). The middle segments of jejunum and ileum, and jejunal mucosa were obtained from healthy and PGR piglets at 42 d of age. Total RNA samples extracted from jejunal mucosa of healthy and PGR piglets were submitted for RNA-seq. Lower villus height was observed in both jejunum and ileum from PGR piglets suggesting structural impairment in small intestine (P < 0.05). RNA-seq libraries were constructed and sequenced, and produced average 4.8 × 107 clean reads. Analysis revealed a total of 499 differently expressed genes (DEGs), of which 320 DEGs were downregulated in PGR piglets as compared to healthy piglets. The functional annotation based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) highlighted that most DEGs were involved in nutrient metabolism and immune responses. Our results further indicated decreased gene expression associated with glucose, lipid, protein, mineral, and vitamin metabolic process, detoxication ability, oxidoreductase activity, and mucosal barrier function; as well as the increased insulin resistance and inflammatory response in the jejunal mucosa of PGR piglets. These results characterized the transcriptomic profile of the jejunal mucosa in PGR piglets, and could provide valuable information with respect to better understanding the nutrition metabolism and immune responses in the small intestine of piglets.

This study was designed to evaluate the antioxidant and anti-inflammatory effects of Eucommia ulmoides flavones (EUF) using diquat-challenged piglet models. A total of 96 weaned piglets were randomly allotted to 1 of 3 treatments with 8 replication pens per treatment and 4 piglets per pen. The treatments were basal diet, basal diet + diquat, and 100 mg/kg EUF diet + diquat. On day 7 after the initiation of treatment, the piglets were injected intraperitoneally with diquat at 8 mg/kg BW or the same amount of sterilized saline. The experiment was conducted for 21 days. EUF supplementation improved the growth performance of diquat-treated piglets from day 14 to 21. Diquat also induced oxidative stress and inflammatory responses and then impaired intestinal morphology. But EUF addition alleviated these negative effects induced by diquat that showed decreasing serum concentrations of proinflammatory cytokines but increasing antioxidant indexes and anti-inflammatory cytokines on day 14. Supplementation of EUF also increased villi height and villous height, crypt depth, but decreased the histopathological score and MPO activity compared with those of diquat-challenged pigs fed with the basal diet on day 14. Results indicated that EUF attenuated the inflammation and oxidative stress of piglets caused by diquat injection.

A previous study has demonstrated that early weaning significantly suppressed hepatic glucose metabolism in piglets. Glutamate (Glu), aspartate (Asp) and glutamine (Gln) are major metabolic fuels for the small intestine and can alleviate weaning stress, and therefore might improve hepatic energy metabolism. The objective of this study was to investigate the effects of administration of Glu, Asp and Gln on the expression of hepatic genes and proteins involved in lipid metabolism in post-weaning piglets. Thirty-six weaned piglets were assigned to the following treatments: control diet (Control; basal diet + 15.90 g/kg alanine); Asp, Gln and Glu-supplemented diet (Control + AA; basal diet + 1.00 g/kg Asp + 5.00 g/kg Glu + 10.00 g/kg Gln); and the energy-restricted diet supplemented with Asp, Gln and Glu (Energy^- + AA; energy deficient diet + 1.00 g/kg Asp + 5.00 g/kg Glu + 10.00 g/kg Gln). Liver samples were obtained on d 5 and 21 post-weaning. Piglets fed Energy^- + AA diet had higher liver mRNA abundances of acyl-CoA oxidase 1 (ACOX1), succinate dehydrogenase (SDH), mitochondrial transcription factor A (TFAM) and sirtuin 1 (SIRT1), as well as higher protein expression of serine/threonine protein kinase 11 (LKB1), phosphor-acetyl-CoA carboxylase (P-ACC) and SIRT1 compared with piglets fed control diet (P < 0.05) on d 5 post-weaning. Control + AA diet increased liver malic enzyme 1 (ME1) and SIRT1 mRNA levels, as well as protein expression of LKB1 and P-ACC on d 5 post-weaning (P < 0.05). On d 21 post-weaning, compared to control group, Glu, Gln and Asp supplementation up-regulated the mRNA levels of ACOX1, ME1 and SIRT1 (P < 0.05). These findings indicated that dietary Glu, Gln and Asp supplementation could improve hepatic lipid metabolism to some extent, which may provide nutritional intervention for the insufficient energy intake after weaning in piglets.

Eucommia ulmoides flavones (EUF) have been demonstrated to attenuate the inflammation and oxidative stress of piglets. This study aimed to test whether EUF could be used as an alternative antibiotic growth promoter to support growth performance and maintain intestinal health in weanling piglets. Weaned piglets (n = 480) were assigned into three groups and fed with a low-protein basal diet (NC), or supplementation with antibiotics (PC) or 0.01% EUF (EUF). Blood, intestinal contents, and intestine were collected on days 15 and 35 after weaning. The results showed the PC and EUF supplementations increased (p < 0.05) body weight on day 35, average daily gain and gain: feed ratio from day 15 to day 35 and day 0 to day 35, whereas decreased (p < 0.05) the diarrhea index of weanling piglets. EUF treatment increased (p < 0.05) jejunal villus height: crypt depth ratio, jejunal and ileal villus height, and population of ileal lactic acid bacteria on day 15 but decreased (p < 0.05) the population of ileal coliform bacteria on day 15 and day 35. These findings indicated the EUF, as the potential alternative to in-feed antibiotic growth promoter, could improve growth performance and intestinal morphology, and decrease colonization of coliform bacteria and diarrhea index in weanling piglets.

Amino acid transporters play an important role in cell growth and metabolism. MeAIB, a transporter-selective substrate, often represses the adaptive regulation of sodium-coupled neutral amino acid transporter 2 (SNAT2), which may act as a receptor and regulate cellular amino acid contents, therefore modulating cellular downstream signaling. The aim of this study was to investigate the effects of MeAIB to SNAT2 on cell proliferation, protein turnover, and the mammalian target of rapamycin (mTOR) signaling pathway in porcine enterocytes. Intestinal porcine epithelial cells (IPEC)-J2 cells were cultured in a high-glucose Dulbecco's modified Eagle's (DMEM-H) medium with 0 or 5 mmoL/L System A amino acid analogue (MeAIB) for 48 h. Cells were collected for analysis of proliferation, cell cycle, protein synthesis and degradation, intracellular free amino acids, and the expression of key genes involved in the mTOR signaling pathway. The results showed that SNAT2 inhibition by MeAIB depleted intracellular concentrations of not only SNAT2 amino acid substrates but also of indispensable amino acids (methionine and leucine), and suppressed cell proliferation and impaired protein synthesis. MeAIB inhibited mTOR phosphorylation, which might be involved in three translation regulators, EIF4EBP1, IGFBP3, and DDIT4 from PCR array analysis of the 84 genes related to the mTOR signaling pathway. These results suggest that SNAT2 inhibition treated with MeAIB plays an important role in regulating protein synthesis and mTOR signaling, and provide some information to further clarify its roles in the absorption of amino acids and signal transduction in the porcine small intestine.

Weaning imposes simultaneous stress, resulting in reduced feed intake, and growth rate, and increased morbidity and mortality of weaned pigs. Weaning impairs the intestinal integrity, disturbs digestive and absorptive capacity, and increases the intestinal oxidative stress, and susceptibility of diseases in piglets. The improvement of intestinal development and health is critically important for enhancing nutrient digestibility capacity and disease resistance of weaned pigs, therefore, increasing their survival rate at this most vulnerable stage, and overall productive performance during later stages. A healthy gut may include but not limited several important features: a healthy proliferation of intestinal epithelial cells, an integrated gut barrier function, a preferable or balanced gut microbiota, and a well-developed intestinal mucosa immunity. Burgeoning evidence suggested nutritional intervention are one of promising measures to enhance intestinal health of weaned pigs, although the exact protective mechanisms may vary and are still not completely understood. Previous research indicated that functional amino acids, such as arginine, cysteine, glutamine, or glutamate, may enhance intestinal mucosa immunity (i.e., increased sIgA secretion), reduce oxidative damage, stimulate proliferation of enterocytes, and enhance gut barrier function (i.e., enhanced expression of tight junction protein) of weaned pigs. A number of feed additives are marketed to assist in boosting intestinal immunity and regulating gut microbiota, therefore, reducing the negative impacts of weaning, and other environmental challenges on piglets. The promising results have been demonstrated in antimicrobial peptides, clays, direct-fed microbials, micro-minerals, milk components, oligosaccharides, organic acids, phytochemicals, and many other feed additives. This review summarizes our current understanding of nutritional intervention on intestinal health and development of weaned pigs and the importance of mechanistic studies focusing on this research area.