Enteral branched-chain amino acids increase the specific activity of jejunal glutaminase and reduce jejunal atrophy

Branched-chain amino acid (BCAA)-enriched nutrient solutions reduce gut atrophy associated with parenteral nutrition. We hypothesized that this effect was mediated by phosphate-dependent glutaminase. Thirty male Wistar rats (300–350 g) underwent a standardized surgical procedure and were then randomized into three groups to receive 6 days of ad libitum enteral nutrition. The animals were fed a solution of conventional nutrients, a solution of conventional nutrients enriched with 2.0% BCAA or a solution of conventional parenteral nutrients enriched with 2.5% glutamine. When compared with rats fed conventional nutrients, rats fed BCAA and glutamine had less jejunal atrophy (P< 0.05) and a greater specific activity of phosphate-dependent glutaminase in the jejunum (131%; P< 0.05). It is concluded that enteral BCAA reduce atrophy of the jejunum via the generation of glutamine.     

The effect of minimum luminal nutrition on mucosal cellularity and immunity of the gut

Many catabolic patients can only consume small volumes of enteral nutrients. The aim of this study was to evaluate markers of cellularity and immunity in the small intestine of rats randomized to receive 6 days of parenteral nutrition, 25% enteral and 75% parenteral nutrition (i.e. minimum luminal nutrition) or enteral nutrition. The same glutamine-enriched solution was used for both parenteral and enteral nutrition. Enteral nutrition was associated with the least amount of jejunal atrophy ( P < 0.01), with the results from the minimum luminal nutrition group approximating those of the parenteral nutrition group. Parenteral nutrition was associated with the greatest number of CD2+ cells ( P < 0.05) and the lowest CD4/CD8 cell ratio ( P < 0.01) in the jejunal mucosa. In essence, we failed to demonstrate that there are any appreciable benefits associated with the enteral consumption of 25% of a nutrient load.     

Influence of glutamine and branched chain amino acids on the jejunal atrophy associated with parenteral nutrition

Infusions of conventional parenteral nutrients (CPN) are associated with gut atrophy. This may be due to the absence of glutamine in such solutions. Although glutamine is a preferred gut nutrient, it is excluded from CPN because it is unstable at room temperature. This problem may be circumvented either directly by the infusion of fresh solutions of glutamine, or indirectly by the infusion of branched chain amino acids (BCAA). We evaluated the effect of infusing either glutamine, BCAA, or glutamine plus BCAA-enriched CPN on the rat jejunum. Sixty male Wistar rats were randomized to receive 6 days of either conventional parenteral nutrition (CPN), CPN plus 1.5% glutamine (GLN), CPN plus 2% BCAA (BCAA), CPN plus 0.8% BCAA and 1.0% glutamine (GLN/BCAA), or a normal oral diet (Chow). Standardized segments of jejunum were then removed for assessment. Compared with the CPN group, both the GLN/BCAA and the BCAA groups had greater mucosal weights (P less than 0.05) and mucosal protein concentrations (P less than 0.05), the GLN/BCAA group had greater jejunal weights (P less than 0.05), and the GLN group had an increased jejunal weight (P less than 0.05) and a higher crypt cell production rate (P less than 0.05). We conclude that the infusion of glutamine or BCAA-enriched parenteral nutrition improves jejunal morphology compared with conventional parenteral nutrition.     

Time Course of Spontaneous Bacterial Translocation from Gastrointestinal Tract and Its Relationship to Intestinal Microflora in Conventionally Reared Infant Rats

Whereas the developed gut mucosal barrier prevents luminal bacteria from invading the host, bacterial translocation appears to be facilitated in the neonate. The aim of this study was to determine the extent to which bacteria spontaneously translocate from the gut to extraintestinal organs during the neonatal period and to relate translocation to the evolving intestinal flora in the rat. Newborn Sprague-Dawley rats suckled ad libitum and ate regular chow after weaning. A total of 167 rats were killed either immediately or at 1, 9, 14, 21, 26, or 42 days after delivery. Mesenteric lymph nodes (MLN), liver, heart blood, and the terminal ileal loop were harvested under sterile conditions and analyzed for aerobic and facultatively anaerobic bacteria by standard microbiologic procedures. Bacterial translocation to the MLN and liver began soon after birth and peaked during the second week. On day 14, translocation to any organ was present in 85% of rats. All cultures from the liver were sterile after day 26. By contrast, the fall in translocation to the MLN was incomplete, as 50% of pups still had positive MLN on day 42. Blood cultures were positive in three of the 167 rats. The intensity of translocation as determined by the number of organs infected significantly increased with the number of gram-negative enterics and gram-positive cocci in the gut and was negatively correlated with the percentage of lactobacilli from the total measured intestinal flora (P < 0.0001). In conclusion, bacterial translocation from the gut is a physiological and age-dependent phenomenon in the neonatal rat. Translocation appears to be facilitated when intestinal concentrations of gram-negative enterics and gram-positive cocci are high and when the concentration of lactobacilli is low.     

Enteral versus parenteral nutrition in acute pancreatitis.

Conventional wisdom has previously dictated that, in order to avoid stimulation of pancreatic secretion during acute pancreatitis, and thus avoid the perpetuation of the enzymatic activation from which the pancreatitis originated, enteral feeding should be avoided. With greater understanding of the potential role of the gastrointestinal tract in the development of a systemic inflammatory response within a number of scenarios, this dogma has recently been challenged. Moreover, there is some evidence to suggest that starving the gastrointestinal tract and providing nutritional support via the parenteral route may be associated with an increased incidence of septic complications. Experimental and clinical evidence suggests that feeding the gut may diminish intestinal permeability to endotoxin and diminish bacterial translocation, thus reducing the cytokine drive to the generalized inflammatory response and preventing organ dysfunction. Preliminary experience suggests that the institution of jejunal (but not gastric or duodenal) nutrition within 48 hours of the onset of severe acute pancreatitis diminishes endotoxic exposure, diminishes the cytokine and systemic inflammatory responses, avoids antioxidant consumption and does not cause the radiological appearances of the pancreas to deteriorate. These observations are paralleled by improvements in clinical outcome measures such as intensive care unit stay, septic complications and mortality. Whist parenteral nutrition continues to have a role in the management of acute pancreatitis particularly when complicated by fistulae or prolonged ileus, the early introduction of jejunal nutrition merits further investigation in acute pancreatitis.     

Effect of prenatal cortisone on spontaneous bacterial translocation from gastrointestinal tract in neonatal rat

The immature host is prone to the passage of bacteria across the gut mucosal barrier. Corticosteroids accelerate the maturation of the intestinal mucosa and alter the composition of the gut bacterial flora. The present study was performed to assess the effect of prenatal cortisone on bacterial translocation in the neonatal rat. Time-pregnant Sprague Dawley rats were randomized on the 19th day of gestation for intraperitoneal injection of either 20 mg/100 g body weight of hydrocortisone or saline. Rats delivered spontaneously and the offspring were suckled ad libitum by the dam. Rat pups (N = 82) were killed 1 or 9 days after delivery. Mesenteric lymph nodes, liver, heart blood, and the terminal ileal loop were excised and quantitatively analyzed for bacteria. After one day, the proportion of rats with positive translocation was not significantly different between the two treatment groups (saline 62%, cortisone 80%, P = NS). By day 9, translocation had increased in the saline group (P = 0.03 vs day 1), did not significantly change in the cortisone group, and was significantly lower in rats treated with cortisone compared with the saline control (saline 90%, cortisone 60%, P = 0.02). The decrease in bacterial translocation after treatment with cortisone was associated with significantly lower total bacterial counts in the ileum (P < 0.05). Cortisone did not reduce bacterial counts in extraintestinal organs with positive translocation. In conclusion, prenatal treatment with cortisone reduces the incidence of spontaneous bacterial translocation from the intestine but not the concentration of translocated bacteria in extraintestinal organs of 9-day-old rats. Cortisone-induced changes of the intestinal microflora may have contributed to the reduction in translocation frequency.     

Changes in intestinal absorption of nutrients and brush border glycoproteins after total parenteral nutrition in rats.

The effect of total parenteral nutrition on nutrients absorption and glycoprotein changes of brush border membrane was examined in rat small intestine. In total parenteral nutrition rats, a marked decrease in activity of brush border enzymes was observed mainly in the proximal and middle segments of the intestine. Galactose perfusion of jejunal segment showed that hexose absorption was significantly inhibited, while intestinal absorption of glycine or dipeptide, glycylglycine was not significantly affected by total parenteral nutrition treatment. When brush border membrane glycoprotein profile was examined by [3H]-glucosamine or [3H]-fucose incorporation into jejunal loops, significant changes were observed in the glycoprotein pattern of brush border membrane especially in the high molecular weight range over 120 kDa after total parenteral nutrition treatment, suggesting strong dependency of glycoprotein synthesis on luminal substances. Molecular weight of sucrase isomaltase in brush border membrane detected by specific antibody showed no significant difference, however, in total parenteral nutrition and control rats. Also, molecular weight of specific sodium glucose cotransporter of intestinal brush border membrane detected by selective photoaffinity labelling was not altered in total parenteral nutrition rats. It may be that prolonged absence of oral food intake may produce significant biochemical changes in brush border membrane glycoprotein and absorptive capacity of small intestine, but these changes were not observed in all brush border membrane glycoproteins.     

Total Parenteral Nutrition Causes Circumferential Intestinal Atrophy,Remodeling of the Intestinal Wall,and Redistribution of Eosinophils in the Rat Gastrointestinal Tract

Total parenteral nutrition (TPN) is held to cause intestinal atrophy and weaken mechanical and immunological barriers. To monitor the degree of atrophy caused by TPN, female Sprague-Dawley rats were, for 8 days, maintained on TPN (n = 6) and compared to identically housed controls given food and water ad libitum (n = 6). Specimens from jejunum, ileum, and colon were taken for histology and morphometric analysis. Topographic distribution and presence of eosinophils, by eosinophil peroxidase (EPO) staining, were examined in the gastric fundus, jejunum, ileum, and colon. Atrophy in terms of a markedly reduced circumference was noted throughout the intestinal tract in all rats subjected to TPN. The width of jejunal and ileal villi was narrowed and the length of jejunal villi was decreased. Furthermore, submucosal thickness in the jejunum and ileum increased. The height of ileal enterocytes remained unaltered. The number of goblet cells decreased in jejunal but not in ileal villi. The Paneth cells, suggested to play important roles in innate defense, increased in size. In the gastric fundus a marked increase in eosinophils was revealed predominantly in the mucosa and submucosa. The number and distribution of jejunal and ileal eosinophils were identical to those of controls. In colon from TPN rats, a redistribution of eosinophils was noted, causing a “band-like” accumulation of eosinophils in the basal portion of the mucosa. In conclusion, TPN causes gut atrophy and an increase in Paneth cell size. Eosinophils increase in number in the gastric fundus and a topographic redistribution occurs in the colon.     

Total parenteral nutrition needs in different types of short bowel syndrome

Thirty-nine patients with short bowel syndrome after extensive small bowel resection, with or without associated partial or total colectomy, received continuous total parenteral nutrition followed by discontinuous parenteral nutrition. Home parenteral nutrition was introduced in 16 of these patients; in eight it was permanent. The assessment of nutritional status included body weight; standard urinary and blood studies; albumin, prealbumin, and transferrin serum levels; and both urinary and fecal nitrogen. A statistically significant correlation (P<0.001) was observed between the length of the remaining small bowel and the necessary duration of nutritional support. Multivariate analysis allowed us to classify patients into three groups as a function of remaining gut length and the duration of required nutritional support. This study should help to define the best nutritional support protocol for patients with various short bowel syndromes in order to ensure the best possible intestinal adaptation and to improve their quality of life.     

A review of the trends in the use of enteral and parenteral nutrition support

This is a review article that discusses the trends in the use of enteral and parenteral nutrition support. Although enteral nutrition has existed longer than parenteral nutrition, only recent data would suggest a clinical benefit of enteral nutrition compared with parenteral nutrition. In this article, indications for parenteral nutrition are listed. Also, data comparing bacterial translocation and complications associated with both forms of nutritional support are discussed. Clinical outcome in specific gastrointestinal diseases is also discussed.     

The Effect of Food Restriction on the Composition of Intestinal Microflora in Rats

The effect of a food-restricted diet on the fecal microflora of rats was studied by determining total anaerobic bacteria, bacterial cellular fatty acids, and the predominant intestinal bacteria shown by polymerase chain reaction (PCR) primers specific for the 16S rRNA gene sequences of 12 bacterial species. Twenty-four female Fischer 344 rats, 57 days old were divided into two groups and maintained on an NIH-31 diet. One group was fed ad libitum while the other group received 60% of ad libitum food intake (40% food restriction supplemented with vitamins and minerals equal to the ad libitum animals). After 2, 10, and 20 weeks on this dietary regimen, groups of four animals were sacrificed and the intestinal contents analyzed for changes in the bacterial flora. The anaerobic population for two-week (short-term) food-restricted rats was 3.2 × 10⁸ per gram, slightly less than the 9.1 × 10⁸ per gram found in the ad libitum-fed rats. The anaerobic populations in 20-week food restricted and ad libitum fed rats were 1.9 × 10⁹ and 2.7 × 10⁹ per gram, respectively. The total anaerobic population did not change significantly in either group during the 20-week study. No statistically significant differences were observed in the bacterial cellular fatty acid profiles between the two groups as determined by gas-liquid chromatography. PCR analysis of the intestinal contents indicated no significant shifts in the predominant flora due to dietary changes. The results, using three different methods to detect changes in the rat intestinal microflora, suggest that long-term dietary restriction had little effect on the microflora of female Fischer 344 rats.     

Effects of incremental starvation on gut mucosa

Starvation induces gut mucosal atrophy, but the effects of progressive dietary restriction are not defined. The study's purpose was to determine the effects of incremental starvation on gut epithelial cell turnover. After food intake of mice was determined, they were divided into five groups: control (ad libitum fed), 75% normal intake, 50% intake, 25% intake, and fasted. Mice were killed after 48 hours, and the proximal small bowel were assessed for weight and protein content. Histologic specimens were examined for villus morphology, apoptosis, and proliferation. After 48 hr of diet restriction, bowel weight decreased in the 50% intake, 25% intake, and fasted groups. Villus density also decreased in the fasted group. Proliferation progressively decreased in the diet-restricted groups. Apoptosis increased in the fasted group, primarily in the villus tip. In conclusion, incremental starvation produces progressive small bowel atrophy. The mechanism involves both decreased gut epithelial cell proliferation and increased apoptosis.     

Alanyl-glutamine provides beneficial nutritional support after orthotopic transplantation of the liver in pigs

We evaluated the nutritional status of pigs that received glutamine after orthotopic liver transplantation. After transplantation, one group of pigs received an oral diet (group I,n=5), one group received conventional total parenteral nutrition (group II,n=4), and one group received alanylglutamine supplemented parenteral nutrition (group III,n=7). We compared nutritional status, graft liver function, and ileal mucosal thickness in the three groups. There were no significant differences in nutritional parameters or serum chemistries among the groups. In terms of ileal integrity, mucosal thickness was reduced after liver transplantation in group II, whereas it was relatively well preserved in group III. The level of endotoxin in the portal venous blood was significantly lower in group III, than in group II on the 7th day after liver transplantation. Parenteral alanyl-glutamine appears to have beneficial effects in preserving the integrity of the ileal mucosa when oral intake of nutrients may not be feasible. This could prevent bacterial translocation in the portal vein.     

<Emphasis Type="Italic">Bifidobacterium adolescentis</Emphasis> Supplementation Ameliorates Parenteral Nutrition-Induced Liver Injury in Infant Rabbits

Background  

Parenteral nutrition (PN)-induced liver injury is associated with gut atrophy, and probiotics have demonstrated the ability to stabilize the intestinal microecosystem and offer protection against bacterial translocation from the gut to the liver. Therefore, we hypothesized that enteral Bifidobacterium supplements could alleviate PN-associated liver injury.     

Effect of folate deficiency and ethanol ingestion on intestinal folate absorption

The effects of folate deficiency, generalized malnutrition, and alcohol ingestion on jejunal transport, mucosal uptake, and reduction of folic acid were evaluated in rats. As measured by an everted gut sac technique, a folate-deficient diet fedad libitum did not alter transport or mucosal uptake of folate. Partial starvation, which was produced in rats pairfed with animals ingesting ethanol, increased jejunal folate transport and mucosal uptake in animals ingesting either a folate-deficient or control diet. A 20% ethanol ingestion by rats consuming folate-deficient or control diets resulted in transport and mucosal uptake rates intermediate in value compared to those fromad libitum fed and pair-fed groups. No differences in reduction of folic acid were found. These results suggest that folate depletion and ethanol ingestion, alone or in combination, do not affect the ability of the rat jejunum to transport folate but that partial starvation results in an increase in folate transport activity.Supported in part by Research Grant AM 14686 and General Research Support Grant 05429 from the USPHS. Dr. Krawitt is the recipient of USPHS Academic Career Development Award K07-35234.     

Regulation of Keratinocyte Growth Factor (KGF) and KGF Receptor mRNAs by Nutrient Intake and KGF Administration in Rat Intestine

The aim of this study was to investigate the regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by diet and KGF treatment in rat intestine. Fasting for three days up-regulated KGF and KGF receptor mRNA levels in ileum and increased KGF receptor mRNA expression in colon. KGF and KGF receptor mRNA levels returned toward control values with ad libitum refeeding but remained elevated when refeeding was limited to 25% of ad libitum intake. KGF treatment during nutrient repletion did not alter intestinal KGF mRNA levels but increased KGF receptor mRNA abundance in ileum and colon. We conclude that the increase in KGF and KGF receptor mRNAs induced by malnutrition may be an adaptive response to attenuate gut mucosal atrophy in this setting. The gut-trophic effects of KGF treatment may be mediated, in part, by up-regulation of the KGF receptor mRNA in small bowel and colon.     

Enteral nutrition and infection in the intensive care unit

Nutritional support of critically ill patients is important since adverse effects of malnutrition are multiple and common. Nutrition via the enteral route is often preferred over central venous or total parenteral nutrition due to its relative ease of administration, lower cost, and infrequent association with severe complication. Enteral nutrition and infection are related. Infectious complications of sepsis and nosocomial pneumonia can occur, but enteral nutrition also may be important in maintenance of normal gut structure and function, thereby decreasing bacterial translocation and the risk of systemic infection.     

Influences of enteral nutrition combined with probiotics on gut microflora and barrier function of rats with abdominal infection

AIM: To investigate the influences of enteral, parenteral nutrition and probiotics delivered by gut on intestinal microecology, epithelial tight junctions, immune and barrier function of rats with abdominal infection. METHODS: Rat abdominal infection models established with cecal ligation and perforation method, were divided into three groups: parenteral nutrition (PN group, n = 7), PN enteral nutrition (EN group, n = 7) and PN EN probiotics (probiotics group, n = 7) via the needle jejunostomy and neck vein for five days. The total nutritional supplement of the three groups was isonitrogenic and isocaloric. Probiotics was delivered by jejunostomy 10 mL/d (1×108 cfu/mL). The rats were killed on the sixth day. The feces in the cecum were cultured for anaerobic bacterial growth and analyzed with bacterial group DNA fingerprint profile with random amplified polymorphic DNA. The transmembrane binding proteins (occludin) and IgA level in plasma cells of intestine epithelium in colon and terminal ileum were measured by an immunohistochemistry method. The ultrastructure of intestinal epithelial tight junctions in colon and small intestine was observed by electron-microscopy. Vena cava blood and the homogenated tissue of liver, lung and mesenteric lymph nodes were cultured to determine the bacterial translocations, and endotoxin in the blood from portal vein was detected. RESULTS: (1) The amount of bacteria of gut species in EN group and probiotic group was higher than that in PN group. The DIMA-profiles in EN group and probiotic group were similar to that of normal rats. The number of DNA-profiles in probiotics group was much more than that in PN group and EN group. Moreover, there were strange stripes in PN group. (2) The expression of occludin and IgA in the small and large intestine in EN group (2.309±0.336, 15.440±2.383) and probiotic group (2.938±0.515, 16.230±3.183) was improved as compared with PN group (1.207±0.587, P < 0.05, 11.189±2.108, P < 0.01). The expression of occludin in probiotic group (intestine: 2.93±0.515; cecum: 3.40±0.617) was higher than that in EN group (intestine: 2.309±0.336; cecum: 2.076±0.670; P < 0.05). The expression of IgA, especially in EN group (intestine: 15.440±2.383) and probiotic EN group (large intestine: 12.516±1.542) significantly increased as compared with PN group (intestine: 11.189±2.108; cecum: 10.160±1.643; P < 0.01). The intestinal epithelial tight junctions and microvilli of the probiotic group were more intact than those in the PN group. (3) The bacterial translocations in blood, liver, lung and mesenteric lymph nodes, and the levels of endotoxin were significantly reduced in probiotic (0.082±0.029) and EN (0.125±0.040) groups as compared with PN group (0.403±0.181, P < 0.05). CONCLUSION: Application of EN combined with probiotics could improve the expression of transmembrane binding proteins (occludin) and IgA, correct the intestinal flora disturbance, maintain gut barrier functions and tight junctions, and reduce the occurrence of gut bacterial translocation.     

Immunonutrition and enteral hyperalimentation of critically ill patients

Physicians need to be maximally aggressive in their use of total enteral nutrition (TEN) in the critically ill patient, due to its lower cost, better physiology, and lower complication rate when compared to parenteral therapy. Various components in TEN such as glutamine, arginine, RNA nucleotides, omega-3 fish oils, and fiber, may have important roles in immunonutrition by maintaining gut integrity, stimulating the immune system, and preventing bacterial translocation from the gut. For each patient, the physician must choose the optimal enteral formula for that particular disease or organ failure state to maximize nutrient substrate assimilation and tolerance. Total parenteral nutrition (TPN) should be used only when a true contraindication to enteral feedings exists or as adjunctive therapy when full nutritional requirements cannot be met by TEN alone.