A high-protein formula increases colonic peptide transporter 1 activity during neonatal life in low-birth-weight piglets and disturbs barrier function later in life.

Dietary peptides are absorbed along the intestine through peptide transporter 1 (PepT-1) which is highly responsive to dietary protein level. PepT-1 is also involved in gut homeostasis, both initiating and resolving inflammation. Low-birth-weight (LBW) neonates are routinely fed a high-protein (HP) formula to enhance growth. However, the influence of this nutritional practice on PepT-1 activity is unknown. Intestinal PepT-1 activity was compared in normal-birth-weight (NBW) and LBW piglets. The effect of HP v. normal-protein (NP) formula feeding on PepT-1 activity and gut homeostasis in LBW piglets was evaluated, during the neonatal period and in adulthood. Flux of cephalexin (CFX) across the tissue mounted in Ussing chambers was used as an indicator of PepT-1 activity. CFX flux was greater in the ileum, but not jejunum or colon, of LBW than NBW piglets during the neonatal period. When LBW piglets were formula-fed, the HP formula increased colonic CFX during the 1st week of life. Later in life, intestinal CFX fluxes and barrier function were similar whether LBW pigs had been fed NP or HP formula. However, colonic permeability of HP- but not NP-fed pigs increased when luminal pH was brought to 6·0. The formyl peptide N-formyl methionyl-leucyl-phenylalanine conferred colonic barrier protection in HP-fed piglets. Heat shock protein 27 levels in the colonic mucosa of HP-fed LBW pigs correlated with the magnitude of response to the acidic challenge. In conclusion, feeding a HP formula enhanced colonic PepT-1 activity in LBW pig neonates and increased sensitivity of the colon to luminal stress in adulthood.

Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe deer.

BACKGROUND: Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. RESULTS: Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric) or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva) which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. CONCLUSIONS: Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins) compared with Roe deer species. CCK and gastrin could play an important role in the regulation of pancreatic secretion in Roe deer as in calf. This work, to the best of our knowledge is the first study which compared the Roe deer adaptation to diet with a domesticated animal largely studied.

Maternal Supplementation of Food Ingredient (Prebiotic) or Food Contaminant (Mycotoxin) Influences Mucosal Immune System in Piglets.

The early life period is crucial for the maturation of the intestinal barrier, its immune system, and a life-long beneficial host-microbiota interaction. The study aims to assess the impact of a beneficial dietary (short-chain fructooligosaccharides, scFOS) supplementation vs. a detrimental dietary environment (such as mycotoxin deoxynivalenol, DON) on offspring intestinal immune system developmental profiles. Sows were given scFOS-supplemented or DON-contaminated diets during the last 4 weeks of gestation, whereas force-feeding piglets with DON was performed during the first week of offspring life. Intestinal antigen-presenting cell (APC) subset frequency was analyzed by flow cytometry in the Peyer's patches and in lamina propria and the responsiveness of intestinal explants to toll-like receptor (TLR) ligands was performed using ELISA and qRT-PCR from post-natal day (PND) 10 until PND90. Perinatal exposure with scFOS did not affect the ontogenesis of APC. While it early induced inflammatory responses in piglets, scFOS further promoted the T regulatory response after TLR activation. Sow and piglet DON contamination decreased CD16+ MHCII+ APC at PND10 in lamina propria associated with IFNγ inflammation and impairment of Treg response. Our study demonstrated that maternal prebiotic supplementation and mycotoxin contamination can modulate the mucosal immune system responsiveness of offspring through different pathways.

Maternal short-chain fructooligosaccharide supplementation influences intestinal immune system maturation in piglets.

Peripartum nutrition is crucial for developing the immune system of neonates. We hypothesized that maternal short-chain fructooligosaccharide (scFOS) supplementation could accelerate the development of intestinal immunity in offspring. Thirty-four sows received a standard or a scFOS supplemented diet (10 g scFOS/d) for the last 4 weeks of gestation and the 4 weeks of lactation. Colostrum and milk immunoglobulins (Ig) and TGFß1 concentrations were evaluated on the day of delivery and at d 6 and d 21 postpartum. Piglet intestinal structure, the immunologic features of jejunal and ileal Peyer's patches, and mesenteric lymph node cells were analysed at postnatal d 21. Short-chain fatty acid concentrations were measured over time in the intestinal contents of suckling and weaned piglets. Colostral IgA (P<0.05) significantly increased because of scFOS and TGFß1 concentrations tended to improve (P<0.1). IFNγ secretion by stimulated Peyer's patch and mesenteric lymph node cells, and secretory IgA production by unstimulated Peyer's patch cells were increased (P<0.05) in postnatal d 21 scFOS piglets. These differences were associated with a higher proportion of activated CD25+CD4α+ T cells among the CD4+ helper T lymphocytes (P<0.05) as assessed by flow cytometry. IFNγ secretion was positively correlated with the population of activated T lymphocytes (P<0.05). Total short-chain fatty acids were unchanged between groups during lactation but were higher in caecal contents of d 90 scFOS piglets (P<0.05); specifically propionate, butyrate and valerate. In conclusion, we demonstrated that maternal scFOS supplementation modified the intestinal immune functions in piglets in association with increased colostral immunity. Such results underline the key role of maternal nutrition in supporting the postnatal development of mucosal immunity.

Maternal 18:3n-3 favors piglet intestinal passage of LPS and promotes intestinal anti-inflammatory response to this bacterial ligand.

We recently observed that maternal 18:3n-3 increases piglet jejunal permeability. We hypothesized that this would favor intestinal lipopolysaccharide (LPS) passage and alter gut immune system education toward this bacterial ligand. Sows were fed 18:3n-3 or 18:2n-6 diets throughout gestation and lactation. In each litter, two piglets were given oral Gram-negative spectrum antibiotic from post-natal day (PND) 14 to 28. All piglets were weaned on a regular diet at PND28. 18:3n-3 piglets exhibited greater jejunal permeability to FITC-LPS at PND28. Levels of 18:3n-3 but neither 20:5n-3 nor 20:4n-6 were greater in mesenteric lymph nodes (MLN) of 18:3n-3 piglets. Jejunal explant or MLN cell cytokine responses to LPS were not influenced by the maternal diet. Antibiotic increased jejunal permeability to FITC-LPS and lowered the level of 20:5n-3 in MLN, irrespective of the maternal diet. At PND52, no long-lasting effect of the maternal diet or antibiotic treatment on jejunal permeability was noticed. 18:3n-3 and 20:4n-6 levels were greater and lower, respectively, in MLN of 18:3n-3 compared to 18:2n-6 piglets. IL-10 production by MLN cells in response to LPS was greater in the 18:3n-3 group, irrespective of the neonatal antibiotic treatment. IL-8 secretion by jejunal explants in response to LPS was lower in antibiotic-treated 18:3n-3 compared to 18:2n-6 piglets. Finally, proportion of MHC class II(+) antigen-presenting cells was greater in 18:3n-3 than 18:2n-6 MLN cells. In conclusion, maternal 18:3n-3 directs the intestinal immune response to LPS toward an anti-inflammatory profile beyond the breastfeeding period; microbiota involvement seems dependent of the immune cells considered.

Defatted bovine colostrum-supplemented diet around weaning improves exocrine pancreatic secretion by means of volume, digestive enzymes, and antibacterial activity.

OBJECTIVES: Exocrine pancreatic secretion contributes to limit pathogenic bacteria-associated diarrhea. Bovine colostrum, used in the treatment of diarrhea, reduces symptoms originating from gut pathogenic bacteria overgrowth. We hypothesized that bovine colostrum may stimulate the exocrine pancreatic secretion. METHODS: Eighteen piglets fitted with 2 permanent catheters (for pancreatic juice collection and reintroduction) were allocated to 1 of the following 2 dietary treatments for 5 days: a control diet or a diet supplemented with defatted bovine colostrum. Pancreatic juice was collected daily, and digestive enzyme activities and antibacterial activity were determined. RESULTS: The prandial pancreatic juice outflow, the basal and prandial lipase output, and the basal secretion of the antibacterial activity were, respectively, 60% (P = 0.08), 154% (P = 0.08), 92% (P = 0.06), and 72% (P < 0.05) higher in piglets fed a diet supplemented with defatted bovine colostrum. CONCLUSIONS: With defatted bovine colostrum, the increased antibacterial activity secretion against Escherichia coli may limit pathogenic bacteria overgrowth of the gut and reduce diarrheal episodes. The role of secretin in the increased pancreatic juice flow and lipase secretion was considered.

Weaning and feed intake alter pancreatic enzyme activities and corresponding mRNA levels in 7-d-old piglets.

We investigated the changes in the capacity for synthesis of the exocrine pancreas of piglets during the 2 wk after weaning at 7 d of age (trial 1) by measuring the expression of digestive enzymes at mRNA and activity levels in pancreas homogenates, and the effects of high and low feed intakes during the 1st wk postweaning (trial 2) on these measures. The trypsin mRNA level was transiently decreased 43% 3 d postweaning (P < 0.05). Thereafter, trypsin and lipase mRNAs linearly increased (P < 0.05). During the 1st wk postweaning, trypsin- and lipase-specific activities were reduced 44 and 79% (P < 0.05), respectively, whereas 14 d after weaning, trypsin was at the preweaning value and lipase was at a low level. Amylase-specific activity did not change with weaning. Plasma cholecystokinin (CCK) and gastrin concentrations decreased 1 d postweaning and increased afterward up to 3 and 5 d postweaning, respectively. By 3 d after weaning, the mRNA level of trypsin was twofold higher (P < 0.05) in piglets that consumed more feed than in those that consumed less, whereas 7 d after weaning, the groups did not differ. By 7 d after weaning, the specific activity of amylase was higher, and lipase-specific activity was lower, in piglets that consumed more feed than in those that consumed less. Plasma CCK and gastrin concentrations measured 7 d after weaning were correlated with feed intake (r = +0.56 and r = +0.68, P < 0.05, respectively). In conclusion, by 3 d postweaning, pancreatic exocrine function was adapting to the new diet. Afterward, the expression of specific genes coding digestive enzymes and the levels of pancreatic enzyme activities were restored or stimulated, except for lipase-specific activity. Therefore, the pancreas can adjust to weaning and dry food intake as early as wk 2 of life.

Small intestine growth and morphometry in piglets weaned at 7 days of age. effects of level of energy intake.

Two trials involving a total of 56 pigs were conducted to examine the effects of weaning at 7 d of age (trial 1) and of energy intake level and length of post-weaning underfeeding period (trial 2) on small intestinal (SI) development and morphometry. At 3 d after weaning, weight of the SI and mucosa (g/kg body weight) and villous height along SI were reduced by 20, 36 and 41%, respectively, compared to the day of weaning. Intestinal morphometrical changes are dependent on SI site and days post-weaning. Villous atrophy on d 3 and recovery on d 14 post-weaning were greater and occurred earlier in the proximal than in the medial and distal SI. Villous height was dependent on the level of energy intake which explains 56% of the variations in proximal SI villous height in weaned pigs and 73% when data of the sow-reared pigs were included in the analysis. Moreover, after 4 d of refeeding, underfed piglets showed similar villous characteristics to piglets fed a continuously high feeding level after weaning stressing that capacities of intestinal restoration were not affected by the length of the post-weaning underfeeding period. Overall, the present results suggest a spatial and temporal effect of weaning on villous atrophy and recovery, and that the level of energy intake is a major factor accounting for the post-weaning villous height.