Enteric and serological distribution of serotonin and its precursor tryptophan in perinatal low and normal weight piglets.

Perinatal mortality is high among small-for-gestational age (SGA) piglets and continues to be an economic burden and threat to animal welfare. As the physiological role of serotonin (5-hydroxytryptamine, 5-HT) in perinatal development and gastrointestinal function in the pig remains unknown, the aim of this study was to assess the enteric distribution of 5-HT cells and to determine 5-HT together with its precursor tryptophan in the serum of perinatal normal and SGA piglets. For this purpose, proximal and distal parts of the small intestine (SI) were processed for immunohistochemical analysis to assess the presence of 5-HT endocrine cells. Serum 5-HT was measured with ELISA, whereas its precursor, that is, the free fraction of tryptophan (FFT) together with albumin-bound tryptophan and total tryptophan, were analysed with HPLC in postnatal piglets. In addition, the morphological growth patterns of the different intestinal tissue layers of both normal and SGA piglets were stereologically analysed. The stereological volume density of 5-HT enteroendocrine cells showed a significant interaction effect between age and region. Indeed, the amount of 5-HT cells in both the proximal and distal part of the SI tended to decrease according to age, with the lowest values detected at day 3 postpartum. No differences could be observed related to BW. Interestingly, the serum concentration of 5-HT was higher in normal piglets compared with SGA piglets. Moreover, the ratio of FFT to total tryptophan was significantly affected by age and BW. Normal piglets had, on average, a lower FFT/total tryptophan ratio compared with SGA piglets. An approximate linear decrease was observed with increasing age. Finally, the immaturity of the intestinal system of the SGA piglets was not reflected in altered volume densities of the different intestinal layers. To conclude, although no BW effect could be detected in the distribution of enteric 5-HT cells, serum 5-HT and the ratio of FFT to total tryptophan ratio showed significant differences between normal piglets and their SGA littermates.

Ghrelin in the gastrointestinal tract and blood circulation of perinatal low and normal weight piglets.

Ghrelin, the 'hunger' hormone, is an endogenous growth hormone secretagogue that exerts a wide range of physiological functions. Its perinatal presence suggests that ghrelin might be involved in growth and metabolism processes during intrauterine and postnatal life. Intrauterine growth-restricted (IUGR) neonates have altered endocrine and metabolic pathways because of malnutrition during foetal development. These changes might include an altered gastrointestinal presence of ghrelin cells (GCs). As ghrelin is mainly secreted by the stomach, this altered presence might be reflected in its serum concentrations. Small-for-gestational age (SGA) pigs appear to be a natural occurring model for IUGR children. Therefore, the first aim of this study was to investigate the presence of gastrointestinal GCs expressing active ghrelin in normal weight (NW) foetal and postnatal piglets compared with their SGA littermates using immunohistochemical analysis in combination with stereological methods. Second, total ghrelin serum concentrations of these piglets were analysed with a porcine radioactive immunoassay. In addition, the growth of the gastric pars fundica in the NW and SGA piglets was analysed stereologically. Corresponding with humans and rats, it was shown that opened- and closed-type immunoreactive GCs are distributed along the entire gastrointestinal tract of the perinatal NW and SGA piglets. However, in contrast to the rat's stomach, the porcine GCs do not disperse from the glandular base to the glandular neck during perinatal development. Furthermore, stereological analysis demonstrated that the NW neonates have a higher amount of gastric cells expressing active ghrelin compared with the SGA piglets that could result in higher milk consumption during the neonatal period. This finding is, however, not reflected in total serum ghrelin levels, which showed no difference between the NW and SGA piglets. Moreover, the stereological volume densities of the fundic layers demonstrate a similar growth pattern in the SGA and NW piglets.

Perinatal growth restriction is not related to higher intestinal distribution and increased serum levels of 5-hydroxytryptamin in piglets.

Serotonin [5-hydroxytryptamin (5-HT)] is abundantly present in intestinal enteroendocrine cells and neurons and plays a crucial role in gastrointestinal functions (i.e., motility and mucosal secretion). Increased concentrations of 5-HT and its precursor l-Trp are present in plasma and brain tissues in case of intrauterine growth retardation (IUGR). Therefore, 5-HT might be involved in the impaired gastrointestinal function associated with IUGR. Small-for-gestational-age (SGA) piglets have been widely used as animal model for IUGR. Hence, the density of intestinal 5-HT cells in fetal and neonatal SGA piglets was compared with serotonergic cell density in normal weight (NW) littermates. Furthermore, 5-HT serum concentrations of the neonatal piglets were analyzed. Stereological analysis showed that fetal piglets have higher (P < 0.01) volume densities of 5-HT enteroendocrine cells compared to 3-d-old piglets irrespective of BW. Serum concentrations did not differ in relation to postnatal age (P = 0.637) and BW (P = 0.892). These results contrast with serum and brain 5-HT and l-Trp levels in human and guinea pig SGA individuals and seemingly contest the fact that 5-HT plays an important role in gut impairment in SGA.

Increased intestinal barrier function in the small intestine of formula-fed neonatal piglets.

Within-litter birth weight variation is adversely correlated to piglet survival and postnatal growth. A less efficient epithelial barrier function in light piglets may partly explain this inverse relationship between birth weight and zootechnical performance. A compromised epithelial barrier increases paracellular permeability; consequently, toxins, allergenic compounds, or bacteria may enter systemic circulation and induce inflammatory responses. Dietary effects on function of gut epithelium of piglet are largely unknown. This study investigated epithelial barrier function of the small intestine of normal birth weight (NBW) piglets (1.46 ± 0.10 kg) and low birth weight (LBW) piglets (<1 kg at birth) in relation to their diet. Sixteen pairs of 3-d-old LBW and NBW piglets were randomly assigned to 3 groups: a sow-fed control group euthanized at day 3 of age (SOW3), piglets sow fed until day 10 (SOW10), and formula-fed piglets fed formula from day 3 until day 10 (FOR10). To measure gut permeability, piglets were dosed intragastrically with 0.75 g lactulose/kg BW and 0.3 g mannitol/kg BW 4 h before euthanasia. Urinary sugar excretion was measured using enzymatic spectrophotometry. Irrespective of birth weight, lactulose levels of FOR10 (4.4 ± 2.3 mmol/L) tended to be lower (P = 0.07) than SOW10 (26.4 ± 10.2 mmol/L) indicating a reduced paracellular intestinal permeability in FOR10. This reduction was associated with a 6-fold elevated (P < 0.01) protein expression of occludin, an important tight junction protein, in FOR10 compared to SOW10. Mannitol levels in FOR10 (31.0 ± 18.2 mmol/L) did not differ (P = 0.28) from SOW10 (61.1 ± 10.2 mmol/L). However, shorter villi (P < 0.01) in FOR10 indicated a reduced absorptive capacity. In conclusion, formula feeding caused minor symptoms of gastrointestinal dysfunction compared to sow-fed piglets irrespective of their birth weight.