Low-birth-weight neonates are routinely fed a high-protein formula to promote catch-up growth and antibiotics are usually associated to prevent infection. Yet the effects of such practices on tissue protein metabolism are unknown. Baby pigs were fed from age 2 to 7 or 28 d with high protein formula with or without amoxicillin supplementation, in parallel with normal protein formula, to determine tissue protein metabolism modifications. Feeding high protein formula increased growth rate between 2 and 28 days of age when antibiotic was administered early in the first week of life. This could be explained by the occurrence of diarrhea when piglets were fed the high protein formula alone. Higher growth rate was associated with higher feed conversion and reduced protein synthesis rate in the small intestine, muscle and carcass, whereas proteolytic enzyme activities measured in these tissues were unchanged. In conclusion, accelerated growth rate caused by high protein formula and antibiotics was not supported by increased protein synthesis in muscle and carcass.
Early postnatal nutrition is involved in metabolic programming, an excess of protein being suspected to enhance early growth and the propensity to later develop insulin resistance and type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that excessive protein intake during the suckling period would overstimulate the endocrine pancreas in the short term and alter durably its maturation, contributing to the later disruption of glucose homeostasis. Normal-birth-weight and low-birth-weight piglets were fed isoenergetic formulae providing an adequate-protein (AP, equivalent to sow milk) or a high-protein (HP, +48 %) supply between 7 and 28 d of age and were fed a standard diet until 70 d of age. During the formula-feeding period, the HP formula did not modify postprandial insulin secretion but transiently increased fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR, P < 0·05). Fasting insulin and HOMA-IR were restored to AP piglets' values 1 month after weaning. The structure of the endocrine pancreas was not affected by the protein content of the formula. The weight at birth had no major effect on the studied parameters. We concluded that a high-protein supply during the suckling period does not interfere with insulin secretion and endocrine pancreas maturation in the short term. It has no consequences either on glucose tolerance 1 month after weaning. The present study demonstrated that up-regulation of postprandial insulin secretion is not involved in higher growth observed in piglets fed a HP formula.
Small birth weight and excess of early protein intake are suspected to enhance later obesity risk. The present study was undertaken to determine the impact of neonatal diets differing in protein content on growth, body composition and hormonal status of 70-d-old pigs born with normal weight (NW) or small weight (SW). At 7 d of age, male and female suckled piglets were assigned to the NW (approximately 1·4 kg at birth) or SW (approximately 0·99 kg at birth) groups. They were fed milk replacers formulated to provide an adequate protein (AP) or a high protein (HP) supply for 3 weeks. From weaning to 70 d of age, all animals received ad libitum the same standard diet. Growth rates were higher (P < 0·05) in HP piglets than in AP piglets during formula feeding and remained higher (P < 0·05) only in HP male pigs thereafter. No difference in feed consumption was detected between groups during the periods examined. Carcass lipid content and the relative weight of perirenal adipose tissue did not differ between the AP and HP pigs. Whereas plasma leptin concentration was higher (P < 0·05) in HP pigs than in AP pigs with a marked difference in SW pigs, plasma insulin-like growth factor (IGF)-I concentration and expression of IGF system genes were not affected by the diets. In summary, a HP intake during the suckling period induced an increase in growth rate that persisted only in male pigs during the post-weaning period. This response was not associated with any difference in adiposity parameters in this period.
Our study aimed at investigating the impact of the level of protein in milk formula on intestinal structure, barrier function, and its nervous regulation in normal and LBW neonates using a porcine model. Normal birth weight (NBW) or LBW piglets were fed from d7 to d28 of age either with a high protein (HP) or with an adequate protein (AP) formula or stayed with their mother [mother fed (MF)]. The proximal jejunum and distal ileum were sampled at d28 for morphometry analysis and ex vivo permeability measurement in Ussing chambers. Formula feeding induced a trophic effect on the jejunum and ileum of both NBW and LBW piglets, which exhibited longer villi than MF animals, irrespective of the type of formula. In NBW piglets, intestinal permeability was not altered by formula feeding. On the contrary, LBW piglets fed with HP formula, but not AP, exhibited a greater ileal permeability than MF piglets. Feeding the HP formula also disturbed jejunal and ileal regulation of permeability by acetylcholine and vasoactive intestinal peptide (VIP) in LBW compared with MF LBW piglets. In conclusion, the level of protein in formulas did not modify intestinal structure and function in NBW individuals but dramatically modified intestinal barrier function physiology in LBW individuals.
High dietary threonine extraction by the digestive tract suggests that threonine contributes to maintain gut physiology. In the present study, we evaluated the impact of a low (6.5 g of threonine/kg diet; LT group) or a control well-balanced threonine diet (9.3 g of threonine/kg diet; C group) given to piglets for 2 weeks on ileal permeability and Na+-dependant glucose absorption capacity in Ussing chambers. The paracellular permeability was significantly increased in the ileum of LT compared to C piglets (P=.017). The Na+-dependent glucose absorption capacity showed a nonsignificant increase in the LT piglets. In addition, we analysed ileal gene expression profiles in the LT and C groups using porcine multitissue cDNA microarrays. Compared to the C piglets, the expression of 324 genes was significantly modified in the ileum of the LT piglets: 214 genes were overexpressed (145 annotated) and 110 were down-expressed (79 annotated). Among them, some are involved in immune and defense responses, energy metabolism and protein synthesis. Furthermore, microarray analysis highlights changes in the expression of the gene encoding for the sodium/glucose cotransporter (SGLT1) and of genes involved in the regulation of paracellular permeability (ZO-1, cingulin and myosin light chain kinase). In conclusion, our results indicate that a moderate threonine deficiency affects intestinal functionality.
Although dietary content of tryptophan has been related to variations of feed intake in lactating sows, the mechanisms remain to be elucidated. Twenty multiparous crossbred Landrace × Large White sows were used to assess variations of tryptophan metabolism around farrowing. Sows were fed 3 kg/d of a standard gestation diet from insemination until farrowing. They were then fed ad libitum a standard lactation diet until weaning. Sows were catheterised on day 70 of gestation and blood samples were drawn on day 37 before parturition, daily during the week before and the week after farrowing, and on days 14 and 21 of lactation. Plasma concentrations of amino acids, kynurenine, niacin, haptoglobin, urea, and vitamin B6 concentration in red blood cells were determined. During the week following parturition, plasma tryptophan and niacin decreased while plasma kynurenine increased (p < 0.05). On the 2nd and 3rd weeks of lactation, plasma tryptophan and kynurenine returned to pre-farrowing concentrations, while niacin increased throughout lactation (p < 0.05). Vitamin B6 increased progressively during the week after farrowing (p < 0.05) and remained constant at a high concentration thereafter. The average feed intake of the sow during lactation was positively correlated with the mean concentrations of niacin (r(2) = 0.25; p < 0.001) and kynurenine (r(2) = 0.31; p < 0.001) in plasma and with vitamin B6 in red blood cells (r(2) = 0.68; p < 0.001). This study suggests that tryptophan catabolism presumably through the kynurenine pathway is high during the 1st week after farrowing, and that dietary supply of niacin and vitamin B6 could be transiently suboptimal in early lactation.
Fumonisin B(1) (FB1) alters intestinal epithelial cell cycle and absorptive, secretory, and barrier properties in vitro, but in vivo data are lacking. Therefore, we tested the hypothesis that repeated intake of a corn culture extract rich in fumonisins, mainly in FB1, alters indices of intestinal absorptive and secretory physiology and barrier function in vivo. Intra-litter pairs of pigs (n = 36) weaned at 28 d, were fed the vehicle (control) or the extract (providing 1.5 mg FB1/kg body weight) daily for 9 d starting 7 d postweaning. After slaughter, the jejunal mucosa of pigs was mounted in Ussing chambers (UC). Extract consumption for 9 d decreased the gain:feed ratio (P = 0.04) and increased liver weight (P = 0.01). Basal net ion secretion (P = 0.02), sodium-dependent glucose absorption (P = 0.02), and theophylline-induced secretion (P < 0.01) of the jejunal mucosa determined in UC were higher in pigs fed the extract than in controls. By contrast, jejunal permeability to the horseradish peroxidase model protein in UC was not influenced by extract consumption. Ileal villi tended to be longer (P = 0.07) and jejunal aminopeptidase N activity was lower (P < 0.01) in pigs fed the extract. In conclusion, consumption of an extract rich in fumonisins for 9 d has the potential to alter intestinal physiology, villous architecture, and enzyme activities. Underlying mechanisms remain to be investigated.
Sodium butyrate (SB) provided orally favours body growth and maturation of the gastrointestinal tract (GIT) in milk-fed pigs. In weaned pigs, conflicting results have been obtained. Therefore, we hypothesised that the effects of SB (3 g/kg DM intake) depend on the period (before v. after weaning) of its oral administration. From the age of 5 d, thirty-two pigs, blocked in quadruplicates within litters, were assigned to one of four treatments: no SB (control), SB before (for 24 d), or after (for 11-12 d) weaning and SB before and after weaning (for 35-36 d). Growth performance, feed intake and various end-point indices of GIT anatomy and physiology were investigated at slaughter. The pigs supplemented with SB before weaning grew faster after weaning than the controls (P < 0.05). The feed intake was higher in pigs supplemented with SB before or after weaning (P < 0.05). SB provided before weaning improved post-weaning faecal digestibility (P < 0.05) while SB after weaning decreased ileal and faecal digestibilities (P < 0.05). Gastric digesta retention was higher when SB was provided before weaning (P < 0.05). Post-weaning administration of SB decreased the activity of three pancreatic enzymes and five intestinal enzymes (P < 0.05). IL-18 gene expression tended to be lower in the mid-jejunum in SB-supplemented pigs. The small-intestinal mucosa was thinner and jejunal villous height lower in all SB groups (P < 0.05). In conclusion, the pre-weaning SB supplementation was the most efficient to stimulate body growth and feed intake after weaning, by reducing gastric emptying and intestinal mucosa weight and by increasing feed digestibility.
Although amino acids (AA) synthesized by enteric microbiota in the upper gut of nonruminants can be absorbed, they do not necessarily make a net contribution to the host's AA supply. That depends on whether protein or nonprotein nitrogen sources are used for microbial protein production. We determined the contributions of urea, endogenous protein (EP), and dietary protein (DP) to microbial valine (M.VAL) at the distal ileum of growing pigs, based on isotope dilutions after a 4-d continuous infusion of l-[1-(13)C]valine to label EP and of [(15)N(15)N]urea. Eight barrows were assigned to either a cornstarch and soybean meal-based diet with or without 12% added fermentable fiber from pectin. Dietary pectin did not affect (P > 0.10) the contributions of the endogenous and DP to M.VAL. More than 92% of valine in microbial protein in the upper gut was derived from preformed AA from endogenous and DP, suggesting that de novo synthesis makes only a small contribution to microbial AA.
Dans cette étude, nous avons évalué l’influence d’une exposition répétée à la fumonisine B1 (FB1) sur les fonctions d’absorption, de sécrétion et de barrière intestinales. Des paires de porcelets (n = 36) de mêmes portées, sevrés et âgés de 35 jours, ont reçu une solution de FB1 (1,5 mg/kg de poids vif/jour) ou le véhicule (témoin) pendant 9 jours. Les performances ont été enregistrées. Après l’abattage des porcs (jour 44), divers organes ont été pesés et des échantillons d’intestin grêle ont été prélevés pour effectuer des mesures de morphologie, d’activités enzymatiques (aminopeptidase N, saccharase), et de physiologie intestinale sur des muqueuses jéjunales montées en chambres d’Ussing (CU). L’ingestion de FB1 n’a pas influencé la croissance mais l’indice de consommation a été plus élevé chez les porcs exposés à FB1 comparativement aux porcs témoins (P = 0,04). Le poids du foie a augmenté (P = 0,01) et celui de la rate a diminué (P = 0,06) avec l’ingestion de FB1. Les villosités iléales tendaient à être plus hautes (p = 0,07) et l’activité jéjunale de l’aminopeptidase N a été plus faible (P = 0,004) chez les porcs ayant reçu la FB1. L’absorption du glucose et la capacité sécrétoire induite par le peptide intestinal vasoactif ou la théophylline en CU avaient tendance à être plus élevées chez les porcs ayant reçu la FB1 que chez les témoins (P = 0,06, 0,10 et 0,07, respectivement). En conclusion, l’ingestion de FB1 altère les fonctions barrière et digestive de l’intestin, ce qui pourrait accroître la sensibilité aux infections entériques.
Background: Although full-term infants suffering intrauterine growth restriction (IUGR) are routinely fed high-protein (HP) formulas to ensure catch-up growth, the effects of HP intake are poorly understood. An IUGR piglet model provides an opportunity to investigate these effects. Methods and Results: Twelve IUGR piglets were artificially fed HP formulas (50% more protein in comparison to sow milk) from the 2nd day of life (d2) until d28. Unexpectedly, all HP piglets developed poor growth, severe hypotonia and polypnea between d10 and d16. One third died spontaneously. This syndrome was investigated to understand its pathophysiology and to adopt a strategy to restore health. Blood and urine biochemistry and amino acid concentrations were investigated in 10 HP piglets and 8 piglets that were fed a normal-protein (NP) formula. In comparison to NP piglets, HP piglets showed significant hypokalemia (2.7 ± 0.6 vs. 3.6 ± 0.6 mmol/l; p < 0.01), hypophosphatemia (1.5 ± 0.2 vs. 3.0 ± 0.3 mmol/l; p > 0.01), hypercalcemia (3.0 ± 0.3 vs. 2.5 ± 0.2 mmol/l; p < 0.01), hyperammonemia (365 ± 4 vs. 242 ± 15 µmol/l; p < 0.05), elevated blood urea (6.5 ± 0.4 vs. 1.3 ± 0.4 mmol/l; p < 0.01) and elevated taurine concentrations (50.2 ± 8.5 vs. 17.7 ± 2.7 µmol/l; p < 0.01). Conclusions: These altered parameters indicated inadequate potassium and phosphorus dietary supplies in HP piglets. When the HP formula was supplemented with monocalcium phosphate and monopotassium phosphate (HP-sup), serum biochemistry was normalized in piglets fed this formula (n = 8). This experimental strategy restored growth in IUGR piglets fed HP-sup, without a toxic effect. The current findings suggest that use of an HP formula without a proportional increase in its phosphorus and potassium content induces pathology similar to the refeeding syndrome in IUGR piglets.
Small birth weight and excess of early protein intake are suspected to enhance later adiposity. The present study was undertaken to determine the impact of diets differing in protein content on short-term growth, adipose tissue development, and the insulin-like growth factor (IGF) system in piglets. Normal (NW) and small (SW) birth weight piglets were fed milk-replacers formulated to provide an adequate (AP) or a high protein (HP) supply between 7 and 28 d of age. The fractional growth rate was higher (p < 0.01) in SW than in NW piglets. At 7 d of age, the lower (p < 0.05) weight of perirenal adipose tissue relative to body mass in SW than in NW piglets did not involve significant changes in plasma IGF-I, leptin, or insulin-like growth factor binding protein levels, but involved differences (p < 0.05) in the expression of IGF-I and leptin in adipose tissue. Growth rates did not differ between AP and HP piglets. At 28 d of age, HP piglets had lower (p < 0.001) relative perirenal adipose tissue weight but did not differ clearly from AP piglets with regard to the IGF system. It remains to be determined whether piglets fed such a high protein intake will stay subsequently with a low adiposity.