Glucagon-like peptide 2 has limited efficacy to increase nutrient absorption in fetal and preterm pigs

Exogenous glucagon-like peptide 2 (GLP-2) prevents intestinal atrophy and increases nutrient absorption in term newborn pigs receiving total parenteral nutrition (TPN). We tested the hypothesis that the immature intestine of fetuses and preterm neonates has a diminished nutrient absorption response to exogenous GLP-2. This was accomplished using catheterized fetal pigs infused for 6 days (87-91% of gestation) with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 7) or saline (n = 7), and cesarean-delivered preterm pigs (92% of gestation) that received TPN with GLP-2 (25 nmol.kg(-1).day(-1) iv; n = 8) or saline (n = 7) for 6 days after birth. Responses to GLP-2 were assessed by measuring intestinal dimensions, absorption of nutrients (glucose, leucine, lysine, proline) by intact tissues and brush border membrane vesicles, and abundance of sodium-glucose cotransporter mRNA. Infusion of GLP-2 increased circulating GLP-2 levels in fetuses, but did not increase intestinal mass or absorption of nutrients by intact tissues and brush border membrane vesicles, except for lysine. Administration of exogenous GLP-2 to preterm TPN-fed pigs similarly did not increase rates of nutrient absorption, yet nutrient absorption capacities of the entire small intestine tended to increase (+10-20%, P < 0.10) compared with TPN alone due to increased intestinal mass (+30%, P < 0.05). GLP-2 infusion did not increase sodium-glucose cotransporter-1 mRNA abundance in fetuses or postnatal preterm pigs. Hence, the efficacy of exogenous GLP-2 to improve nutrient absorption by the intestine of fetal and preterm pigs is limited compared with term pigs and more mature animals and humans.     

Link between intestinal immunity and practical approaches to swine nutrition

Gaining a deeper understanding into the underlying mechanisms associated with intestinal function and immunity during the weaning transition is critical to help shed new light into applied nutrition approaches to improve piglet performance and health during this critical life-stage transition. The transient anorexia triggered at weaning leads to compromised intestinal barrier function and a localized inflammatory response. Considering barrier function, specific nutrient fractions appear to have a significant impact on the development and function of the immune and microbial systems around weaning. Understanding the specific impact of nutrients in the small intestine and hindgut is important for helping to bring more focus and consistency to nutritional approaches to support health and immunity during the weaning transition period. The challenge continues to be how to translate these modes of action into practical and scalable approaches for swine nutrition. We will focus specifically on practical nutritional approaches to influence intestinal immunity through lipid, protein and antioxidant nutrition.     

Role of carnitine during development

Fatty acids are an important fuel source for neonates. The utilization of long chain fatty acids as a fuel source is dependent upon adequate concentrations of carnitine. Carnitine also has functions in other physiological processes critical to the survival of the neonate such as lipolysis, thermogenesis, ketogenesis, and possibly regulation of certain aspects of nitrogen metabolism. Plasma and tissue carnitine concentrations in neonates are depressed compared with those of older individuals. The capability for carnitine biosynthesis is much less in the neonate than in the adult. Human milk contains carnitine and appears to be the major source of carnitine to meet the neonate's metabolic needs. However, total parenteral nutrition solutions and soy-based infant formulas contain no carnitine. Evidence is accumulating that all infant diets may need to supply carnitine to meet the neonate's metabolic needs.     

Do northern bobwhite quail modulate intestinal nutrient absorption in response to dietary change? A test of an adaptational hypothesis

We acclimated northern bobwhite quail (Colinus virginianus) to either chow (high carbohydrate/low protein) or crickets (low carbohydrate/high protein) and tested predictions of hypotheses based on the premise of the economical design of animals. The adaptive modulation hypothesis predicts that d-glucose uptake would be higher and l-proline uptake lower in bobwhites acclimated to chow. The spare capacity hypothesis predicts that the capacity to absorb d-glucose actively will exceed the estimated nutrient load from daily food intake. There was no significant dietary effect on intestinal d-glucose (P = 0.8) and l-proline (P = 0.7) uptake rates measured in vitro using the everted sleeve technique. In chow eaters maximal mediated d-glucose uptake summed along the entire length of intestine (53 cm) was far too low (7.2 mmol/d) to explain observed rates of glucose absorption in vivo (>35 mmol/d). Hence, both predictions were falsified. In vitro uptake may not be an appropriate measure of the intestine's absorptive capacity because it does not measure possibly important pathways of passive absorption. There is increasing evidence that substantial passive glucose absorption occurs in some birds. If passive absorption predominates the adaptive modulation hypothesis might not apply.     

Allometry of paracellular absorption in birds

Water-soluble nutrients can be absorbed across the intestinal epithelium by transcellular and paracellular processes. Recent studies suggest that small birds (<180 g) have more extensive paracellular absorption of glucose than nonflying mammals. This may be a feature that compensates for a reduced small intestine size because small birds have smaller mass-corrected intestinal length than do nonflying mammals, but the difference diminishes in larger birds. We hypothesized that if this explanation were correct, there would be a negative correlation between paracellular absorption and body mass in birds and that larger birds would have paracellular absorption comparable to that of nonflying mammals. We tested this hypothesis, using consistent methodology, by measuring the extent of absorption of a series of inert carbohydrate probes in heavier bird species (>300 g) selected from diverse taxa: American coots, mallards, pheasants, and pigeons. Absorption of carbohydrate probes was inversely related to body mass in birds, and absorption of these probes in large birds (>500 g) was comparable to absorption measurements in nonflying mammals. Higher paracellular uptake in the smaller avian species may offer a physiologically inexpensive means of nutrient absorption to compensate for a reduced small intestine size but may make those species more vulnerable to toxicant absorption.     

Paracellular absorption: a bat breaks the mammal paradigm

Bats tend to have less intestinal tissue than comparably sized nonflying mammals. The corresponding reduction in intestinal volume and hence mass of digesta carried is advantageous because the costs of flight increase with load carried and because take-off and maneuverability are diminished at heavier masses. Water soluble compounds, such as glucose and amino acids, are absorbed in the small intestine mainly via two pathways, the transporter-mediated transcellular and the passive, paracellular pathways. Using the microchiropteran bat Artibeus literatus (mean mass 80.6+/-3.7 g), we tested the predictions that absorption of water-soluble compounds that are not actively transported would be extensive as a compensatory mechanism for relatively less intestinal tissue, and would decline with increasing molecular mass in accord with sieve-like paracellular absorption. Using a standard pharmacokinetic technique, we fed, or injected intraperitoneally the metabolically inert carbohydrates L-rhamnose (molecular mass = 164 Da) and cellobiose (molecular mass = 342 Da) which are absorbed only by paracellular transport, and 3-O-methyl-D-glucose (3OMD-glucose) which is absorbed via both mediated (active) and paracellular transport. As predicted, the bioavailability of paracellular probes declined with increasing molecular mass (rhamnose, 90+/-11%; cellobiose, 10+/-3%, n = 8) and was significantly higher in bats than has been reported for laboratory rats and other mammals. In addition, absorption of 3OMD-glucose was high (96+/-11%). We estimated that the bats rely on passive, paracellular absorption for more than 70% of their total glucose absorption, much more than in non-flying mammals. Although possibly compensating for less intestinal tissue, a high intestinal permeability that permits passive absorption might be less selective than a carrier-mediated system for nutrient absorption and might permit toxins to be absorbed from plant and animal material in the intestinal lumen.     

Research on the therapeutics of intense abdominal irradiations in pigs

Summary Tests of surgical treatments (graft of small intestine, and partial enter ectomy before or after irradiation) and dietetic treatments (continuous parenteral feeding) were carried out on 80 pigs irradiated over the posterior half of the body with doses of between 950 and 1750 rad at mid plane.The results relate to clinical symptoms, survivals, haematology, and histopathology; nutritional aspects were studied by means of evaluation of balances (nitrogen, lipids, and minerals) and absorption tests (⁵⁸Co - Vit. B 12 and iodised lipids).Above 1200 rad recuperation of the digestive system did not in general make prolonged survival possible; in addition to intestinal lesions, renal and especially pancreatic atrophy appeared, whose consequences appeared to be determinative as regards the nutrition and hence the survival of the animals.     

Does the natural diet influence the intestine's ability to regulate glucose absorption?

Summary Two fish species (rainbow trout and common carp) that differ in natural diet also exhibit differences in the adaptive flexibility of their intestinal nutrient transport mechanisms in response to changes in dietary nutrient composition. When carp ingested a feed that was 24% glucose by weight, there was an increase in both the intestinal length and rates of nutrient absorption, particularly for glucose, when compared to carp fed an isonitrogenous diet devoid of digestible carbohydrate. As a result, the intestine's uptake capacity (nmol of glucose and proline absorbed per min per g body weight) was higher in carp fed the 24% glucose feed. Due to the greater increase in glucose uptake, the ratio of glucose uptake relative to proline (G/P ratio) was higher in carp fed the 24% glucose. Thus, carp are able to adapt to the quantity, and apparently also to the type, of digestible carbohydrate in the diet. In contrast, glucose uptake by trout was unresponsive to the quantity of dietary carbohydrate. Insted, the elevated glucose paradoxically resulted in a greater uptake capacity for proline and a lower G/P ratio. Hence, the adaptive capabilities of the intestinal nutrient transport processes are matched to the potential variation in the carbohydrate content of the natural diet.Abbreviation PEG polyethylene glycol     

Glutamine-enriched parenteral nutrition regulates the activity and expression of intestinal glutaminase

The aim of this study was to examine the effect of glutamine-enriched parenteral nutrition on the activity, expression and distribution of glutaminase mRNA within the small intestine of rats. Central venous lines were inserted into 30 male Wistar rats before they were fed for 6 days with either: (a) conventional parenteral nutrition, (b) 2.5% glutamine-enriched parenteral nutrition, or (c) rat food ad libitum. Jejunal glutaminase activity per milligram of dry matter was greatest in the animals fed rat food (0.94+/-0.29), intermediate in the glutamine supplemented rats (0.69+/-0.19) and least in the rats nourished with conventional parenteral nutrition (0.55+/-0.24) (P<0.05). The data for glutaminase expression exhibited a similar trend (P<0.05). In situ hybridisation analysis confirmed that glutaminase is expressed in the mucosa along the whole length of the small intestine. It was concluded that provision of glutamine alters the activity and expression of glutaminase in intestinal enterocytes. The results suggest that glutamine increases glutaminase activity by promoting the accumulation of intestinal glutaminase mRNA.     

Nutrition, infection and child growth in Papua New Guinea

Growth patterns of populations in Papua New Guinea (PNG) have traditionally shown considerable variation, with the greatest difference lying between coastal and highland populations. While genetic differences in explaining these patterns cannot be excluded, the generally poor growth relative to western growth references is largely due to the complex interactive effects of undernutrition and infection. The effects of diet, nutrition and infection on the nutritional status of a child vary with age, the general disease ecology and the type and extent of exposure to it, patterns of infant and young child feeding, and types of food consumed. There are two possible ways in which the relationship between undernutrition and infection can begin; one in which poor nutritional status leads to impaired immunocompetence and reduced resistance to infection, and the other in which exposure to infectious disease can lead to a range of factors that reduce food intake, absorption of nutrients, or increase nutrient requirements. In PNG prior to, and at early stages of modernisation, primary malnutrition is likely to have been the usual initiating factor in the onset of growth faltering due to undernutrition-infection interactions. However, the possibility that infection may have been the initiating event in some societies cannot be excluded. This would have happened by way of early dietary supplementation of infants with foods of minor nutritional significance, which could have acted as a vehicle for the introduction of infectious disease to the child. With modernisation and adoption of primary health care principles, earlier supplementation of infant diet than was previously the case became common in PNG. This has lead to general improvements in growth and nutritional status. However, in populations where undernutrition is still common, infection has become more important than primary malnutrition as the initiator of growth faltering due to undernutrition-infection interactions.     

Intestinal microflora and obesity in rats

The relationship was evaluated between early nutritional experiences, the intestinal microflora and the small intestinal functions in the mechanism of predisposition to obesity development. Male Sprague-Dawley rats were used in which the quantity of nutrition was manipulated from birth to weaning (day 30) by adjusting the number of pups in the nest to 4 small litters (SL) and 10 normal litters (NL) and fed a standard diet from days 30 to 40 of age. After 40 d, the postnatally overfed SL pups became heavier, displayed significantly enhanced adiposity, body mass gain and food intake as well as a significantly higher jejunal alkaline phosphatase and maltase activity than in rats nursed in NL nests. The effect of different early nutrition was also accompanied by the appearance of significantly decreased Bacteroides and significantly increased enterococci and lactobacilli of obese rats than in lean NL rats. The amounts of Bacteroides were negatively correlated with fat pad mass, body mass, body-mass gain and food intake whereas enterococci and lactobacilli were correlated positively with the same parameters. Our results demonstrate that postnatal nutritional experience may represent a predisposing factor influencing ontogeny of small intestine function and development of intestinal microbial communities. The acquired changes and associated alterations in food digestion could be a component of regulatory mechanisms contributing to the development of obesity and its maintenance in later life.     

Delayed effects of protein deficiency in nutrition of the pregnant rats on development of the enzymatic system in digestive and nondigestive organs of offspring

It has been found for the first time that protein deficit in female's nutrition during prenatal development of the offspring is accompanied by considerable changes in the activity of intestinal digestive enzymes and of the same hydrolases in the colon, liver and kidneys both in early and in late ontogenesis. It seems possible that changes of the small intestine enzyme functions and hydrolytic functions of other digestive and non-digestive organs in result of an unfavorable early "metabolic/nutritional programming" may be crucial in disorders of metabolic processes leading to development of diseases of risk in adult life.     

Gut-trophic feed additives and their effects upon the gut structure and intestinal metabolism. State of the art in the pig, and perspectives towards humans

The correct functional development of the gastrointestinal tract is of special importance during the neonatal and weaning phases of reared piglets. Nutrition is obviously a critical determinant in the growth of the gut in the young swine. The mucosal epithelium of the small intestine is reputed anatomically and functionally immature in neonatal pigs, a feature that appears to be exacerbated at weaning, when a colonization of the gut occurs by "new" microorganisms entering the alimentary canal with the solid feed. This frequently exposes piglets to diarrhoeic syndromes and other intestinal disturbances. Functional feed additives, also called nutraceuticals, appear as promising alternative substances to the use of chemotherapeutics as growth promoters in the rearing farm, above all considering the near banning of them by the European Parliament in the view of reducing antibiotic resistance phenomena in human therapies. Several feed additives are available that may play a role in the pig nutritional plan because of their trophic and cyto-protective effects on the gastrointestinal apparatus. Paying special attention to the quantitative consequences (histometry) upon the gut of the examined dietary supplements, this review, even if not fully exhaustive, will focus on the function (and possibly the mechanism/s of action) of certain gut-trophic nutrient substrates. This in turn will sustain the potential use of these substances in human therapy, especially the one directed at resolving intestinal diseases, both in adult and infant ages. In nutritional studies as well as in other biomedical research fields, the swine is an excellent animal model.     

Contributions of nutrition science to anthropological research.

Certain investigations of nutrition scientists have demonstrated the effects of cultural practices on nutrient intake. Anthropologists, too, have studied diets and food-related behavior, although until recently their interests infrequently included nutritional status. In the last decade, nutrition scientists' research helped stimulate the creation of an interdisciplinary specialty, nutritional anthropology, that combines techniques from both nutritional and anthropological science in the study of food use in relation to health. Practitioners of this expanding field make useful contributions to research in human nutrition through study of social aspects of the diet of individuals and groups. Their assistance can be particularly helpful in studies of populations in developing countries and of ethnic minorities in this country. Certain unanswered nutritional questions, which might more readily be solved by the combined efforts of nutritionists and nutritional anthropologists than by either professional alone, are presented.     

Effect of infection on nutritional status.

All infections no matter how mild decrease nutrient intakes and increase nutrient losses even when subclinical. The losses include decreased intestinal absorption, direct loss of nutrients in the gut, internal diversion for metabolic responses to infection and increased BMR when fever is present. Infection influences in this way not only protein and energy status but also that of most other nutrients. The clinical importance of these consequences of infection depends on the prior state of the individual, the nature and duration of the infection and the diet of the individual during the infection, particularly dietary intake during the convalescent period and whether full recovery takes place before another infection occurs. In industrialized countries particular attention must be paid to the nutrition of hospitalized patients since they are frequently debilitated by their primary disease, morbidity, and their nutritional status. Morbidity and mortality are increased by nosocomial infections to which the poorly nourished individual is more susceptible.     

Transition from parenteral to enteral nutrition induces immediate diet-dependent gut histological and immunological responses in preterm neonates

Necrotizing enterocolitis (NEC) in preterm infants develops very rapidly from a mild intolerance to enteral feeding into intestinal mucosal hemorrhage, inflammation, and necrosis. We hypothesized that immediate feeding-induced gut responses precede later clinical NEC symptoms in preterm pigs. Fifty-six preterm pigs were fed total parenteral nutrition (TPN) for 48 h followed by enteral feeding for 0, 8, 17, or 34 h with either colostrum (Colos, n = 20) or formula (Form, n = 31). Macroscopic NEC lesions were detected in Form pigs throughout the enteral feeding period (20/31, 65%), whereas most Colos pigs remained protected (1/20, 5%). Just 8 h of formula feeding induced histopathological lesions, as evidenced by capillary stasis and necrosis, epithelial degeneration, edema, and mucosal hemorrhage. These immediate formula-induced changes were paralleled by decreased digestive enzyme activities (lactase and dipeptidylpeptidase IV), increased nutrient fermentation, and altered expression of innate immune defense genes such as interleukins (IL-1α, IL-6, IL-18), nitric oxide synthetase, tight junction proteins (claudins), Toll-like receptors (TLR-4), and TNF-α. In contrast, the first hours of colostrum feeding induced no histopathological lesions, increased maltase activity, and induced changes in gene expressions related to tissue development. Total bacterial density was high after 2 days of parenteral feeding and was not significantly affected by diet (colostrum, formula) or length of enteral feeding (8-34 h), except that a few bacterial groups (Clostridium, Enterococcus, Streptococcus species) increased with time. We conclude that a switch from parenteral to enteral nutrition rapidly induces diet-dependent histopathological, functional, and proinflammatory insults to the immature intestine. Great care is required when introducing enteral feeds to TPN-fed preterm infants, particularly when using formula, because early feeding-induced insults may predispose to NEC lesions that are difficult to revert by later dietary or medical interventions.     

Effect of structured lipid-enriched total parenteral nutrition in rats bearing yoshida sarcoma

The efficacy of structured lipid, a triacylglycerol of medium and long chain fatty acids, as an element of nutritional support therapies in cancer cachexia was investigated. Using the Yoshida sarcoma to induce cachexia, male Sprague Dawley rats (90 g) were injected subcutaneously with tumor cells (n = 17) or sterile saline (n = 16). Seven days later, rats were randomized to two intravenous diets for 3 days at 220 kcal/kg body weight/d, including 2 g nitrogen/kg body weight/d and 39% of total calories as either structured lipid or long chain triglyceride. Nitrogen balance, tumor growth rate, energy metabolism, and plasma albumin and free fatty acid levels were measured, and whole-body protein kinetics and liver, muscle, and tumor fractional protein synthetic rates were evaluated by adding (14)C-leucine to the diet during the last 4 hours of feeding. Nitrogen balance improved (P < .05) in both tumor and control rats receiving structured lipid-enriched total parenteral nutrition, and was also greater in tumor rats compared with controls. There were no differences in tumor growth or protein kinetics between diet groups. Albumin was lower (P < .05) in tumor rats, but significantly higher in both tumor and control rats given structured lipid-enriched total parenteral nutrition. Free fatty acid was significantly higher in tumor rats versus controls. Whole-body protein kinetics were similar among the four groups. Liver weight, liver weight to body weight ratio, and liver protein synthetic rate were higher in tumor rats. Also, liver weight to body weight ratio was lower in tumor and control animals given structured lipid-enriched total parenteral nutrition. Muscle protein synthetic rate was significantly lower in tumor rats, but higher in tumor and control rats given long chain triglyceride-enriched total parenteral nutrition. The nutritional benefits of structured lipid-enriched total parenteral nutrition favor support of host tissue without promoting tumor growth.     

The influence of estradiol and diet on small intestinal glucose transport in ovariectomized rats

Although gender differences exist for intestinal absorption of nutrients and drugs, the possible role estradiol may play in modulating nutrient transport has not been established. Therefore, small intestine glucose transport was measured 1 week after administering estradiol to ovariectomized rats fed diets high in carbohydrate (C) or protein (P). Rats treated with estradiol ate 21% less (P<0.05) and lost body mass (7%; P<0.05) but did not have smaller intestines. Administration of estradiol increased rates of glucose transport, but only when the rats were fed the C diet. These findings indicate that estradiol causes a disconnect between food intake and the dimensions and nutrient transport capacities of the small intestine. Furthermore, the responses to estradiol are influenced by diet composition, are not of the same magnitude for rats and dogs, and can be predicted to affect systemic availability of nutrients and drugs.     

The role of neuropeptides in caterpillar nutritional ecology

Plant diet strongly impacts the fitness of insect herbivores. Immediately, we think of plant defensive compounds that may act as feeding deterrents or toxins. We are, probably, less aware that plants also influence insect growth and fecundity through their nutritional quality. However, most herbivores respond to their environment and select the diet which optimizes their growth and development. This regulation of nutritional balance may occur on many levels: through selecting and ingesting appropriate plant tissue and nutrient digestion, absorption and utilization. Here, we review evidence of how nutritional requirements, particularly leaf protein to digestible carbohydrate ratios, affect caterpillar herbivores. We propose a model where midgut endocrine cells assess and integrate hemolymph nutritional status and gut content and release peptides which influence digestive processes. Understanding the effects of diet on the insect herbivore is essential for the rational design and implementation of sustainable pest management practices.