The role of exocrine pancreas for feed intake and growth. Studies in a model with exocrine pancreatic insufficient young pigs.

Exocrine pancreatic insufficiency (EPI), resulting from disease (e.g. cystic fibrosis, chronic pancreatitis) or surgery (e.g. pancreectomy or pancreas duct ligation), leads to disorders in the digestive system, such as, maldigestion, malabsorption and finally malnutrition. Pancreatic duct-ligated (PDL) pigs have been used as a suitable large-animal model to study the conditions and treatment of EPI. The main objectives of this thesis were to highlight the role of the exocrine pancreas in the growth and performance of young mammals. For that reason the EPI-pig model was evaluated and tested. The results showed a difference in the response to induced EPI by duct-ligation of different-aged pigs. Pigs that underwent PDL at an age of 7 weeks showed arrested growth, while pigs that underwent PDL at 16 weeks showed normal growth. Dietary supplementation with a porcine pancreatic enzyme preparation (PEP) restored growth of pigs. Moreover, dietary supplementation with PEP stimulated feed intake and growth in un-operated pigs. To evaluate the role of the exocrine pancreas for nutrient utilization, pigs were infused with an elemental diet (mimicking a digested diet) either alone or with oral PEP supplementation. Although the elemental diet was sufficient in maintaining normal growth in intact pigs, EPI-pigs showed growth arrest even the elemental diet was given. However, oral PEP supplementation partially restored the growth of these EPI-pigs infused with the elemental diet. This indicates that the exocrine pancreas, in addition to its digestive function, affects nutrient utilization by improving anabolism in young rapid-growing pigs. The changes of the gut in EPI pigs were manifested by increased intestinal permeability and increase of mucin-producing cells in jejunum. Moreover, in pigs duct-ligated at 7 weeks of age the gut morphology showed decrease of stomach mucosa in fundus and atrophy of the intestinal mucosa, while gut morphology of older pigs, ligated at 16 weeks of age, were similar to un-operated intact pigs. These results suggest that intestinal absorptive capacity was reduced in younger, but not in older EPI pigs. However, the brush border disaccharidases activities and non-pancreatic hydrolases-like activities in the small intestine were similar in both of these groups. In addition, the gut-associated lymphoid tissue appear to enhance only in older EPI pigs In conclusion, the EPI pig model conclusively shows the important role of exocrine pancreatic function for performance of fast-growing animals. The exocrine pancreas function is indispensable in early life but its importance decreases with age. Apart from the digestive function, the exocrine pancreas plays an essential role in post-absorptive nutrient utilization in young pigs. The compensatory mechanisms to EPI and capacity to digest and absorb the diet are age-related and appear to depend on the maturity of the gut

Growth is dependent on the exocrine pancreas function in young weaners but not in growing-finishing pigs

A correlation between the exocrine pancreatic function and growth has been previously demonstrated in growing pigs but the data are inconsistent. This was investigated by studying the growth performance of pigs with exocrine pancreatic insufficiency (EPI) at different ages and maintained under similar conditions. Twelve 7 week old (10.5 +/- 1.3 kg) weaners, and twelve 16 week old (43 +/- 5 kg) growing-finishing pigs were used in the experiments, and 6 pigs from each group were operated and pancreatic duct-ligated. Starting at 3-5 weeks after the operation, when EPI had developed, weekly recordings of feed consumption and growth were done before, during and after feed supplementation with porcine pancreatin (Creon (R) 10000). In weaner pigs, EPI caused growth arrest while it did not affect the growth of older pigs, as compared to respective un-operated groups of pigs. The daily feed consumption (DFC) was lower in the weaner EPI-pigs while it was similar in the growing-finishing EPI-pigs, as compared to un-operated pigs. Feed supplementation with Creon (R) improved the DFC and growth in both the EPI and un-operated pigs. In conclusion, the results showed the importance of the exocrine pancreatic function for growth in weaner pigs, while in older animals it played a minor role in growth. Feed supplementation with pancreatin increased the appetite and ensured an improved feed conversion

Effects on gut properties in exocrine pancreatic insufficient (EPI) pigs, being growth retarded due to pancreatic duct ligation at 7 weeks but not at 16 weeks of age.

Exocrine pancreatic insufficiency (EPI) induced in young pigs by pancreatic duct ligation (PDL) early after weaning result in total growth deprivation while it has little effect in somewhat older pigs. The main objective was to study effects of EPI on gut structure and function in littermate pigs underwent to PDL at different age

The effect of long-term lactobacilli (lactic acid bacteria) enteral treatment on the central nervous system of growing rats

The aim of this study was to explore the relationship between Consumption of large doses of lactic acid bacteria (LAB) and the behaviour and brain morphobiochemistry of normal growing rats. Four groups of rats were treated with LAB Cultures twice daily for 6 months. The control group received 1 ml of saline per treatment, while two experimental groups received I nil of living bacteria (Lactobacillus plantarum and Lactobacillus fermentum, respectively) and the remaining group received a heat-treated (inactivated) L. fermentum culture. After 2 and 6 months of treatment, respectively, eight animals from each group were sacrificed, and specimens were taken for further analyses. The behaviour of the rats was evaluated five times in an open-field test at monthly intervals throughout the study. Lactobacilli treatment for 2 months induced changes in the motoric behaviour of the rats. The concentration of the astrocytesoluble and filament glial fibrillary acidic protein (GFAP) decreased in the posterior part of the hemispheres, including the thalamus, hippocampus and cortex of the rats treated with L.fermentum. A greater decrease in filament GFAP (up to 50%) was shown in the group receiving the live from of L. fermentum. In contrast, the GFAP in the live L. plantarum-treated group increased, showing elevated levels of the Soluble and filament forms of GFAP in the posterior part of the hemispheres. A 60-66% decrease in the amount of the astrocyte-specific Ca-binding protein S-100b was shown in the posterior parts of the hemispheres and in the hindbrain of rats given LAB for 2 months. Prolonged feeding with LAB for 4 months up to full adulthood led to a further decrease in astrocytc reaction, reflected as all additional decrease in the amount Of Soluble GEAP and locomotor activity in all experimental groups. The changes in filament GFAP and S-100b appeared to disappear after prolonged feeding (total of 6 months) with LAB. In summary, LAB dietary treatment affected the ontogenetic development of the astrocytes, with the highest intensity observed in the early stages of rat development. It can be postulated that LAB treatment may play a preventive role in neurological diseases by decreasing astrocyte reaction and, consequently, lowering locomotor activity. (C) 2009 Elsevier Inc. All rights reserved

The growth of exocrine pancreatic insufficient young pigs fed an elemental diet is dependent on enteral pancreatin supplementation

Young exocrine pancreas insufficient (EPI) pigs given a commercial feed (polymeric diet) show growth retardation that can be reversed by dietary supplementation with pancreatic enzymes. Our aim was to investigate if providing an elemental diet, mimicking a pre-digested diet, can support body growth in EPI-pigs. Thus, EPI-pigs, pancreatic duct-ligated at 12.2 +/- 2.6 weeks of age (15.3 +/- 4.8 kg), were fed for 6 days either a commercial polymeric pig feed or infused i.v. with an elemental diet, with or without oral supplementation with a porcine enzyme preparation (Creon (R)). The body weight (BW) gain was then compared at day 7. Control pigs (with intact pancreata) showed a 14.0 +/- 1.3% increase in BW independent of the diet, while EPI-pigs given the same diets either lost (polymeric diet) or slightly increased (elemental diet) their BW. In contrast, EPI-pigs fed the polymeric feed with Creon supplementation showed a normalised growth and EPI-pigs given the elemental diet with Creon supplementation gained 8.5 +/- 0.7% in BW. In conclusion, control pigs maintained a normal growth, independently of the diet being given in polymeric or elemental form, while EPI-pigs showed an impaired growth when receiving the same diets without oral enzyme supplementation. This suggests that pancreatic juice or enzyme preparations, in addition to their digestive properties, stimulate nutrient assimilation and anabolic processes in young fast-growing pigs. (C) 2010 Elsevier B.V. All rights reserved

Hormonal and immune profiles in blood were unaffected by PHA provocation in suckling and weaning pigs

The lectin, phytohaemagglutinin (PHA), from red kidney beans has been shown as an inducer of growth and precocious gastrointestinal (Cl) maturation in suckling animals, thus better preparing piglets for the weaning procedure. PHA exposure results in the release of gut peptide hormones and/or activation of the Cl immune system. The aim of this study was to elucidate the mechanisms of PHA provocation by studying changes in the blood/plasma levels of major gut hormones, immune parameters and acute phase proteins. Suckling, 9-10 day-old, littermate piglets were gavage fed PHA, either in purified or crude form or, as a control, alpha-lactalbumin (n = 5-6 pigs/group) and blood was obtained repeatedly during one week and after weaning at 5 weeks. No significant differences in the blood parameters between PHA-treated pigs in comparison to their time-matched controls were found during the first week after treatment. At weaning significant changes in hormonal (insulin) and immune (WBC) parameters and CRP were observed, however, these effects were independent of earlier PHA treatment. In conclusion, PHA, given enterally as a single dose, did not affect the basal blood parameters analysed, during both the suckling and post-weaning periods in piglets. (C) 2010 Elsevier B.V. All rights reserved

An elemental diet fed, enteral or parenteral, does not support growth in young pigs with exocrine pancreatic insufficiency.

BACKGROUND: & aims: Young individuals with exocrine pancreatic insufficiency (EPI) show growth reduction that can be reversed by dietary pancreatic enzyme supplementation. Here we investigated whether feeding an elemental diet could replace the growth-promoting effect of enzyme supplementation in EPI pigs. METHODS: Weaned pigs with intact pancreas (control) or pancreatic duct-ligated (EPI pigs) were given a commercial pig feed, a fat-enriched diet, or an elemental diet, intragastrically and intravenously, with or without porcine pancreatin (Creon((R))) supplementation for 1week. RESULTS: Control pigs, irrespective of receiving pig feed or an elemental diet, increased their body weight by 13.4-20.1%, while EPI pigs showed negligible weight gain. Giving a fat-enriched diet did not improve growth of the EPI pigs. However, if the EPI pigs were supplemented with pancreatin in combination with fat-enriched feed or the elemental diet, i.v., their body weight increased by 16.6 %and 8.5%, respectively. CONCLUSION: Control pigs maintained normal growth, independently of the diet being given in polymeric or elemental form, while EPI pigs showed impaired growth when receiving the same diets without enzyme supplementation. Pancreatic juice and enzyme preparations, in addition to their digestive properties, also appear to affect nutrient assimilation and anabolism in young individuals

Precocious gut maturation and immune cell expansion by single dose feeding the lectin phytohaemagglutinin to suckling rats.

The dietary lectin phytohaemagglutinin (PHA) induces gut growth and precocious maturation in suckling rats after mucosal binding. The present study investigated the dose range in which PHA provokes gut maturation and if it coincided with immune activation. Suckling rats, aged 14 d, were orogastrically fed a single increasing dose of PHA: 0 (control), 2, 10, 50 or 250 mug/g body weight (BW) in saline. The effect on gut, lymphoid organs and appearance of CD3+ (T-lymphocyte) and CD19+ (B-lymphocyte) cells in the small-intestinal mucosa was studied at 12 h (acute) and 3 d (late phase) after treatment. The low PHA doses (2 and 10 mug/g BW) induced intestinal hyperplasia without mucosal disarrangement but did not provoke gut maturation. Only the high PHA doses (50 and 250 mug/g BW) temporarily disturbed the intestinal mucosa with villi shortening and decrease in disaccharidase activities, and later after 3 d provoked precocious maturation, resulting in an increase in maltase and sucrase activities and decrease in lactase activity and disappearance of the fetal vacuolated enterocytes in the distal small intestine. Exposure to the high, but not to the low, PHA doses increased the number of mucosal CD19+ and CD3+ cells in the small intestine after 12 h, a finding also observed in untreated weaned rats aged 21-28 d. In conclusion, there was a dose-related effect of PHA on gastrointestinal growth and precocious maturation that coincided with a rapid expansion of mucosal B- and T-lymphocytes, indicating a possible involvement of the immune system in this process

Pancreatic and pancreatic-like microbial proteases accelerate gut maturation in neonatal rats.

Postnatal gut maturation in neonatal mammals, either at natural weaning or after precocious inducement, is coinciding with enhanced enzymes production by exocrine pancreas. Since the involvement of enzymes in gut functional maturation was overlooked, the present study aimed to investigate the role of enzymes in gut functional maturation using neonatal rats