Arginine Supplementation Induces Arginase Activity and Inhibits TNF‐α Synthesis in Mice Spleen Macrophages After Intestinal Obstruction

Background: The purpose of this study was to assess the effect of arginine supplementation on arginase activity, tumor necrosis factor–α (TNF‐α) and interleukin‐10 (IL‐10) synthesis in cultured splenic macrophages from a murine model of intestinal obstruction (IO). The effects of nitric oxide synthase (iNOS) inhibition were also studied using iNOS knockout animals. Material and Methods: Male C57BL6/J wild‐type (WT) and iNOS knockout (iNOS–/–) mice were randomized into 6 groups: Sham and Sham–/– (standard chow), IO and IO–/– (standard chow + IO), and Arg and Arg–/– (standard chow supplemented with arginine + IO). After 7 days of treatment with standard or supplemented chow, IO was induced. Arginase activity as well as TNF‐α and IL‐10 levels were analyzed in splenic macrophage cultures. Results: Arginine supplementation and the absence of iNOS increased arginase activity in splenic macrophages (Arg, IO–/–, and Arg–/– groups vs the Sham group; P < .05). Arginine was also related to a decrease in TNF‐α levels (Arg vs IO group, P < .05) and maintenance of IL‐10 levels (Arg vs other groups, P > .05). The inhibition of iNOS did not result in effects on the concentration of cytokines (Sham–/–, IO–/–, and Arg–/– vs other, P < .05). Conclusions: Arginine supplementation and iNOS inhibition led to increased arginase activity. Arginine availability decreased plasma TNF‐α levels, which may be directly related to nitric oxide derived from arginine.     

Pretreatment with arginine preserves intestinal barrier integrity and reduces bacterial translocation in mice

ObjectiveTo evaluate the effects of arginine on intestinal barrier integrity and bacterial translocation (BT) in mice undergoing intestinal obstruction.MethodsMice were divided into 3 groups, treated for 7 d before surgical intervention with isocaloric and isoprotein diets. The ARG group received a diet containing 2% arginine, the IO (intestinal obstruction) and Sham groups, standard chow diet. On the eighth day of treatment, all animals received diethylenetriamine pentaacetic acid (DTPA) solution labeled with ^99mTechnetium (^99mTc-DTPA) by gavage for intestinal permeability analysis. After 90 min, the animals were anesthetized and the terminal ileum ligated. The Sham group only underwent laparotomy. After 4, 8, and 18 h, blood was collected for radioactivity determination. Samples of ileum were collected 18 h after surgery for histological analysis. In another set of animals, BT was evaluated. After 7 d of treatment, all animals received 10⁸ CFU/mL of ^99mTc-E.coli by gavage; 90 min later they were submitted to the surgical procedure described above. BT was determined by the uptake of ^99mTc-E.coli in blood, mesenteric lymph nodes, liver, spleen, and lungs, assessed 18 h after the surgery.ResultsThe intestinal permeability and BT were higher in the IO group when compared with the Sham group (P < 0.05). Arginine supplementation reduced intestinal permeability and BT to physiologic levels. Histological analysis showed mucosal ileum preservation in animals treated with arginine.ConclusionArginine was able to preserve barrier integrity, thus reducing BT.     

Pretreatment and Treatment With L‐Arginine Attenuate Weight Loss and Bacterial Translocation in Dextran Sulfate Sodium Colitis

Background: Imbalances in a variety of factors, including genetics, intestinal flora, and mucosal immunity, can contribute to the development of ulcerative colitis and its side effects. This study evaluated the effects of pretreatment or treatment with arginine by oral administration on intestinal permeability, bacterial translocation (BT), and mucosal intestinal damage due to colitis. Methods: C57BL/6 mice were distributed into 4 groups: standard diet and water (C: control group), standard diet and dextran sodium sulfate (DSS) solution (Col: colitis group), 2% L ‐arginine supplementation for 7 days prior to DSS administration and during disease induction (PT: pretreated group), and 2% L ‐arginine supplementation during disease induction (T: treated group). Colitis was induced by administration of 1.5% DSS for 7 days. After 14 days, intestinal permeability and BT were evaluated; colons were collected for histologic analysis and determination of cytokines; feces were collected for measurement of immunoglobulin A (IgA). Results: The Col group showed increased intestinal permeability (C vs Col: P < .05) and BT (C vs Col: P < .05). In the arginine‐supplemented groups (PT and T), this amino acid tended to decrease intestinal permeability. Arginine decreased BT to liver during PT (P < .05) and to blood, liver, spleen, and lung during T (P < .05). Histologic analysis showed that arginine preserved the intestinal mucosa and tended to decreased inflammation. Conclusions: Arginine attenuates weight loss and BT in mice with colitis.     

Glutamine Supplementation Decreases Intestinal Permeability and Preserves Gut Mucosa Integrity in an Experimental Mouse Model

Background: Glutamine (GLN) is the preferred fuel for enterocytes, and GLN supplementation is critical during stressful conditions. The aim of this study was to evaluate the effect of GLN on intestinal barrier permeability and bacterial translocation in a murine experimental model. Methods: Swiss male mice (25–30 g) were randomized into 3 groups: (1) sham group; (2) intestinal obstruction (IO) group; (3) IO and GLN (500 mg/kg/d) group. Two different experiments were carried out to assess intestinal permeability and bacterial translocation. In the first experiment, the animals were divided into the 3 groups described above and received diethylenetriamine pentaacetate radiolabeled with technetium (^99mTc) on the eighth day. At different time points after intestinal obstruction, blood was collected to determine radioactivity. The animals were killed, and the small intestine was removed for histological analyses. In the bacterial translocation study, on the eighth day all groups received Escherichia coli labeled with ^99mTc. After 90 minutes, the animals underwent intestinal obstruction and were killed 18 hours later. Blood, mesenteric lymph nodes, liver, spleen, and lungs were removed to determine radioactivity. Statistical significance was considered when P ≤ .05. Results: The levels of intestinal permeability and bacterial translocation were higher in the IO group than in the sham and GLN groups (P < .05). GLN decreased intestinal permeability and bacterial translocation to physiologic levels in the treated animals and preserved intestinal barrier integrity. Conclusions: GLN had a positive impact on the intestinal barrier by reducing permeability and bacterial translocation to physiologic levels and preserving mucosal integrity.     

Pretreatment with citrulline improves gut barrier after intestinal obstruction in mice

Background: Citrulline has been shown to be an important marker of gut function, regulator of protein metabolism, and precursor of arginine. The authors assessed the effects of citrulline on gut barrier integrity and bacterial translocation (BT) in mice undergoing intestinal obstruction. Methods: Mice were divided into 3 groups: sham, intestinal obstruction (IO), and citrulline (CIT). The CIT group received a diet containing 0.6% citrulline; the IO and sham groups were fed a standard chow diet. On the eighth day of treatment, all animals received a diethylenetriamine pentaacetic acid (DTPA) solution labeled with ^99mTechnetium (^99mTc‐DTPA) by gavage for the intestinal permeability study. Terminal ileum was ligated except the sham group, which only underwent laparotomy. After 4, 8, and 18 hours, blood was collected to determine radioactivity. Samples of ileum were removed 18 hours after intestinal obstruction for histological analysis. In another set of animals, BT was evaluated. Animals received 10⁸ CFU/mL of ^99mTc–Escherichia coli by gavage; 90 minutes later, they underwent ileum ligation. Intestinal fluid and serum were collected to measure sIgA and cytokines. Results: The CIT group presented decreased intestinal permeability and BT when compared with the IO group (P < .05). Histopathology showed that citrulline preserved the ileum mucosa. The sIgA concentration was higher in the CIT group (P < .05). The IO group presented the highest levels of interferon‐γ (P < .05). Conclusions: Pretreatment with citrulline was able to preserve barrier integrity and also modulated the immune response that might have affected BT decrease.     

Enteral Arginine Partially Ameliorates Parenteral Nutrition–Induced Small Intestinal Atrophy and Stimulates Hepatic Protein Synthesis in Neonatal Piglets

Background: Arginine is an indispensable amino acid in neonates; de novo synthesis of arginine occurs in the small intestine (SI) but is reduced during parenteral nutrition (PN), limiting the arginine available to the mucosa. We assessed the effects of route of intake and dietary concentration of arginine on protein synthesis, superior mesenteric artery (SMA) blood flow, and SI morphology. Methods: Piglets (n = 18, 14–17 days old) were given complete PN for 3 days to induce SI atrophy, then switched to 1 of 3 treatments: arginine‐free PN plus an intragastric (IG) infusion of high arginine (1.6 g·kg^?1·d^?1, IG‐H Arg) or low arginine (0.6 g·kg^?1·d^?1, IG‐L Arg) or complete high‐arginine PN (1.6 g·kg^?1·d^?1, IV‐H Arg). Results: Enteral arginine, irrespective of amount provided, stimulated hepatic protein synthesis compared with intravenous delivery of arginine (P = .01). SMA blood flow declined for all groups following the initiation of PN. After 48 hours on the test diets, all groups reached low constant levels, but the IV‐H group was significantly higher than both IG groups (P < .05). Despite greater blood flow, the SI morphological characteristics in IV‐H Arg pigs were not significantly improved over the other groups. IV‐H Arg pigs had higher plasma concentrations of indispensable amino acids (tyrosine, isoleucine, and valine) compared with IG‐H Arg, despite identical amino acid intakes. Conclusions: Intravenous delivery of arginine sustained the best SMA blood flow, whereas even a moderate amount of enteral arginine stimulated liver protein synthesis and maintained SI growth, independent of blood flow.     

The impact of arginine on bacterial translocation in an intestinal obstruction model in rats

BACKGROUND & AIMS: Arginine has been shown to have multiple beneficial metabolic and immunologic effects in stress situations. Supplementation of arginine has been shown to promote wound healing and intestinal mucosal recovery after trauma, ischemia or intestinal resection. Bacterial translocation has also been evaluated although with conflicting results and using different assessing techniques. Therefore, the aim of this study was to evaluate the effects of arginine on bacterial translocation in an intestinal obstruction model in rats using Escherichia coli labeled with 99mTechnetium. METHODS: Male Wistar rats (250-350 g) were randomized to receive conventional chow, diet supplemented with pure arginine or diet supplemented with an immunonutrition enteral formula, enriched with arginine, omega-3 fatty acid and RNA. After 7 days, the animals were anesthetized. Terminal ileum was isolated and a ligature was placed around it. E. coli labeled with 99mTechnetium (99mTc-E. coli) was inoculated into the intestinal lumen (terminal ileum). After 24 h, the animals were sacrificed. Blood, mesenteric lymph nodes (MLN), liver, spleen and lungs were removed for radioactivity determination. RESULTS: Arginine supplementation (300 mg/day, 600 mg/day or present in the enteral formula) reduced the level of bacterial translocation when compared with the control group (p<0.05). This was shown by significantly decrease uptake of 99mTc-E. coli in blood, MLN, liver, spleen and lungs of the animals in the experimental groups (p < 0.05). CONCLUSIONS: These results have shown that arginine was able to decrease bacteria translocation despite intestinal obstruction. There are several mechanisms which might explain the role of arginine and these will be the subject of future studies.     

精氨酸增强全肠外营养对急性胰腺炎大鼠肠粘膜屏障的影响

目的：探讨精氨酸增强精氨酸增强ＴＰＮ对急性胰腺炎（ＡＰ）大鼠肠粘膜屏障的影响。方法：雄性ＳＤ大鼠６４只，随机分成：①对照组（ｎ＝１６）；②ＡＰ组（ｎ＝１６）；③ＡＰ＋ＴＰＮ组（ＴＰＮｓ组ｎ＝１６）；④ＡＰ＋ＴＰＮ＋精氨酸组（ＴＰＮａ组ｎ＝１６）。分别于建立急性胰腺炎模型后第１及第５天剖杀每组８只大鼠取材，检测肠粘膜一氧化氮（ＮＯ）、丙二醛、蛋白质含量、肠系膜淋巴结及门静脉血细菌移位率。结果：与对照组比较，术后１天及５天时，ＡＰ组肠粘膜丙二醛焦点量及肠系膜淋巴结细菌移位率显著升高；５天时蛋白质含量显著降低，而门静脉血细菌移位率明显升高。与ＴＰＮｓ组比较，ＴＰＮａ组１天时肠粘膜ＮＯ含量即明显升高；肠系膜淋巴结细胞移位率显著降低；５天时肠粘膜ＮＯ与蛋白质含量均显著升高；丙二醛含量显著降低。结论：急性胰腺炎可引起肠粘膜     

Effect of arginine on gastrointestinal immunity during total parenteral nutrition

It has been well recognized that the prolonged use of total parenteral nutrition (TPN) leads to intestinal immunodeficiency and bacterial translocation (BT). Arginine (ARG) is known to have immunostimulatory effects. But its effects on gut immunity are unknown. This experiment was designed to evaluate the effects of arginine on gut immunity during TPN. Male Sprague Dowley rats were randomized to three groups: group I (chow) was fed rat chow and water ad libitum, group II (TPN) received a standard formula of TPN and group III (TPN-ARG) received the same formula of TPN as group II with the amino acid composition containing 0.5% arginine. With the duration of TPN, the rates of BT increased and interleukin 2 (IL-2) production decreased in TPN group. The results in TPN-ARG group were partly reversed. When TPN was administered for 2 weeks, the rate of BT decreased significantly (P < 0.05) and IL-2 production increased markedly (P < 0.01) in the TPN-ARG group compared with those in the TPN group. Our results suggest that arginine can decrease BT and increase IL-2 production in rats during prolonged TPN.     

Protection against increased intestinal permeability and bacterial translocation induced by intestinal obstruction in mice treated with viable and heat-killed <Emphasis Type="Italic">Saccharomyces boulardii</Emphasis>

Background  

There are substantial evidences suggesting that probiotics can protect the gastrointestinal tract against inflammatory or infectious episodes. The effects of oral treatment with viable or heat-killed cells of Saccharomyces boulardii (Sb) on bacterial translocation, intestinal permeability, histological aspect of the ileum, and some immunological parameters were evaluated in a murine intestinal obstruction (IO) model.     

Partial Enteral Nutrition Preserves Elements of Gut Barrier Function,Including Innate Immunity,Intestinal Alkaline Phosphatase (IAP) Level,and Intestinal Microbiota in Mice

Lack of enteral nutrition (EN) during parenteral nutrition (PN) leads to higher incidence of infection because of gut barrier dysfunction. However, the effects of partial EN on intestina linnate immunity, intestinal alkaline phosphatase (IAP) and microbiota remain unclear. The mice were randomized into six groups to receive either standard chow or isocaloric and isonitrogenous nutritional support with variable partial EN to PN ratios. Five days later, the mice were sacrificed and tissue samples were collected. Bacterial translocation, the levels of lysozyme, mucin 2 (MUC2), and IAP were analyzed. The composition of intestinal microbiota was analyzed by 16S rRNA pyrosequencing. Compared with chow, total parenteral nutrition (TPN) resulted in a dysfunctional mucosal barrier, as evidenced by increased bacterial translocation (p < 0.05), loss of lysozyme, MUC2, and IAP, and changes in the gut microbiota (p < 0.001). Administration of 20% EN supplemented with PN significantly increased the concentrations of lysozyme, MUC2, IAP, and the mRNA levels of lysozyme and MUC2 (p < 0.001). The percentages of Bacteroidetes and Tenericutes were significantly lower in the 20% EN group than in the TPN group (p < 0.001). These changes were accompanied by maintained barrier function in bacterial culture (p < 0.05). Supplementation of PN with 20% EN preserves gut barrier function, by way of maintaining innate immunity, IAP and intestinal microbiota.     

Effects of Enteral Immunonutrition on the Maintenance of Gut Barrier Function and Immune Function in Pigs With Severe Acute Pancreatitis

Background: This study evaluated the effects of enteral immunonutrition (EIN) supplemented with glutamine, arginine, and probiotics on gut barrier function and immune function in pigs with severe acute pancreatitis (SAP). Methods: The model was induced by retrograde injection of 5% sodium taurocholate and trypsin via the pancreatic duct. After induction of SAP, 18 pigs were randomly divided into 3 groups, in which either parenteral nutrition (PN), control enteral nutrition (CEN), or EIN was applied for 8 days. Serum and pancreatic fluid amylase concentration was determined. Intestinal permeability (lactulose to mannitol ratio) was measured by high‐performance liquid chromatography, and plasma endotoxin was quantified by the chromogenic limulus amebocyte lysate technique. Samples of venous blood and organs were cultured using standard techniques. Pancreatitis severity and villi of ileum were scored according to histopathologic grading. Plasma T‐lymphocyte subsets were measured by flow cytometry, and immunoglobulins (Igs) were determined via enzyme‐linked immunosorbent assay. Results: There were no significant differences in serum and pancreatic fluid amylases concentrations or in pancreatitis severity between any 2 of the 3 groups. Compared with PN and CEN, EIN significantly decreased intestinal permeability, plasma endotoxin concentration, and the incidence and magnitudes of bacterial translocation, but increased ileal mucosal thickness, villous height, crypt depth, and percentage of normal intestinal villi. Significant differences were found in CD3⁺, CD4⁺ lymphocyte subsets, the ratio of CD4⁺: CD8⁺ lymphocyte subsets, and serum IgA and IgG, but not IgM, between any 2 of the 3 groups. Conclusions: EIN maintained gut barrier function and immune function in pigs with SAP.     

Pretreatment With L‐Citrulline Positively Affects the Mucosal Architecture and Permeability of the Small Intestine in a Murine Mucositis Model

Background: Mucositis is a common complication in patients undergoing radiotherapy and chemotherapy. It is associated with pain, poor quality of life, and malnutrition, leading to an increased number of hospital admissions and prolonged hospitalization. The use of immunonutrients may be an alternative treatment option, which may help to improve patient outcome. Objective: Here we assessed the impact of L‐citrulline (CIT) on a murine model of 5‐fluorouracil (5FU)–induced mucositis. Methods: Swiss male mice were randomized into 4 groups: control, CIT, 5FU, and 5FU+CIT. Mice were fed with commercial chow and supplemented with an oral solution of alanine (control and 5FU groups) or CIT (CIT and 5FU+CIT groups). On the seventh day, mice received intraperitoneal phosphate‐buffered saline or 5FU (200 mg/kg, single dose) to induce mucositis. On the 10th day, mice were euthanized, and the blood and small intestines were harvested. Body weight, morphology, histopathology score (hematoxylin and eosin) of the small intestine (from 0–12), myeloperoxidase activity, oxidative stress level, and intestinal permeability were assessed. Results: We observed significant weight loss after the administration of 5FU in both treated and control animals. CIT administration contributed to a partial recovery of the mucosal architecture as well as an intermediate reduction of the histopathologic score, and functional intestinal permeability was partially rescued. Conclusions: CIT administration attenuated 5FU‐mediated damage to the mucosal architecture of the small intestine, decreasing the size of the injured areas and promoting decreased intestinal permeability.     

Effects of Enteral Nutrition on the Barrier Function of the Intestinal Mucosa and Dopamine Receptor Expression in Rats With Traumatic Brain Injury

Background: Impaired intestinal mucosal barrier (IMB) function is common in traumatic brain injury (TBI), but dopamine receptors (DRs) change in intestinal mucosa after TBI, and effects of enteral nutrition (EN) and supplements on IMB function remain unclear. Our purpose was to study the effects of EN and supplements on intestinal mucosal permeability (IMPB) and the expression of DRs DRD1 and DRD2 in the intestinal mucosa of rats with TBI. Methods: Forty‐eight rats were divided into 8 groups; control, animals with TBI, dopamine group, animals with TBI treated with dopamine antagonist, EN alone, or EN combined with glutamine, probiotics, or a combination of probiotics and glutamine daily after TBI. Results: The IMPB was improved in the glutamine, probiotics, and combination groups. Including probiotics improved IMPB more than adding glutamine, and bacterial translocation in the intestines after TBI was reduced in the probiotics and combination groups (all Ps < .01). TBI led to elevated DRD1 and DRD2 mRNA and protein levels, which were reduced in the DA antagonist, glutamine, probiotics, and combination groups. DRD2 mRNA and protein levels in the probiotics and combination groups were decreased more than in the DA antagonist group (all Ps < .01). The increased IMPB after TBI correlated with increased DRD1 and DRD2 levels in the rat intestinal mucosa. Conclusion: EN supplemented with probiotics or combining glutamine and probiotics lowers the increased IMPB, bacterial translocation, and DRD1 and DRD2 mRNA and protein expression in rat intestinal mucosa caused by TBI.     

The effect of immunonutrition on bacterial translocation,and intestinal villus atrophy in experimental obstructive jaundice

BACKGROUND & AIMS: Spontaneous bacterial infection and septicemia due to increased bacterial translocation (BT) in patients with obstructive jaundice result in significant morbidity and mortality. The present study evaluates the effects of enteral nutrition with immune enhancing feeds on BT and intestinal villus histopathology promoted by obstructive jaundice. METHODS: Fifty male Wistar-albino rats weighing 250-300g were assigned into five equal groups of 10. Animals in Groups I, II, and III were fed with standard chow, those in Group IV were given glutamine 1g/kg/day and the remaining 10 animals in Group V were fed with an arginine, omega-3 fatty acids, and RNA-supplemented enteral diet for (1g/kg/day amino acid and 230 kcal/kg) 7 days preoperatively. Group I underwent sham operation and the remaining animals in all other groups underwent common bile duct ligation. After operation, Group I had standard chow, Groups II and IV had glutamine, Groups III and V had an arginine omega-3 fatty acids, and RNA-supplemented enteral diet for 7 days. All animals were sacrificed on the 8th postoperative day and evaluated both biochemically and histopathologically. Samples from blood, liver, mesenteric lymph nodes and spleen were cultured under aerobic conditions. RESULTS: Significantly less BT was observed in groups fed with an arginine, omega-3 fatty acids, and RNA-supplemented enteral diet or glutamine in pre-and postoperative periods as compared to others (P<0.001). Histologic evaluation also showed significant reduction in villus atrophy in these groups. CONCLUSIONS: Enteral immunonutrition using glutamine or arginine, omega-3 fatty acids, and RNA-supplemented enteral diet during both pre-and postoperative periods seems to reduce BT and decrease atrophy of intestinal mucosal villi in rats with obstructive jaundice.     

Glutamine Improves Innate Immunity and Prevents Bacterial Enteroinvasion During Parenteral Nutrition

Background: Patients receiving parenteral nutrition (PN) are at increased risk of infectious complications compared with enteral feeding, which is in part explained by impaired mucosal immune function during PN. Adding glutamine (GLN) to PN has improved outcome in some clinical patient groups. Although GLN improves acquired mucosal immunity, its effect on innate mucosal immunity (defensins, mucus, lysozymes) has not been investigated. Methods: Forty‐eight hours following venous cannulation, male Institute of Cancer Research mice were randomized to chow (n = 10), PN (n = 12), or PN + GLN (n = 13) for 5 days. Small intestine tissue and luminal fluid were collected for mucin 2 (MUC2), lysozyme, cryptdin 4 analysis, and luminal interleukin (IL)–4, IL‐10, and IL‐13 level measurement. Tissue was also harvested for ex vivo intestinal segment culture to assess tissue susceptibility to enteroinvasive Escherichia coli. Results: In both luminal and tissue samples, PN reduced MUC2 and lysozyme (P < .0001, respectively) compared with chow, whereas GLN addition increased MUC2 and lysozyme (luminal, P < .05; tissue, P < .0001, respectively) compared with PN alone. PN significantly suppressed cryptdin 4 expression, while GLN supplementation significantly enhanced expression. IL‐4, IL‐10, and IL‐13 decreased significantly with PN compared with chow, whereas GLN significantly increased these cytokines compared with PN. Functionally, bacterial invasion increased with PN compared with chow (P < .05), while GLN significantly decreased enteroinvasion to chow levels (P < .05). Conclusions: GLN‐supplemented PN improves innate immunity and resistance to bacterial mucosal invasion lost with PN alone. This work confirms a clinical rationale for providing glutamine for the protection of the intestinal mucosa.     

Surgical Anatomy Does Not Affect the Progression of Intestinal Failure–Associated Liver Disease in Neonatal Piglets

Background: Intestinal failure–associated liver disease (IFALD) causes significant morbidity in neonates with short bowel syndrome (SBS) dependent on parenteral nutrition (PN). Resected ileum, with loss of the ileocecal valve (ICV), is the most common anatomy in SBS, yet its impact on IFALD has not been adequately studied. Methods: Neonatal piglets were randomized to 75% intestinal resection with jejunocolic anastomosis (JC, n = 12), 75% resection with jejunoileal anastomosis and intact ICV (JI, n = 13), PN‐fed sham (sham, n = 14), or sow‐fed control (SF, n = 8). Surgical and sham piglets received 100% PN for 14 days before bile flow was measured and blood chemistry, liver pathology, jejunal permeability, and bacterial translocation were assessed. Results: Bile flow was lower for PN‐fed compared with SF (P = .002) but not different between the PN‐fed groups. Total bilirubin (P = .03) and liver pathology (P < .001) were greater in PN‐fed than SF groups but not different between PN‐fed groups. Serum bile acids were increased in sham (P = .01) but not different between SBS groups. PN‐fed piglets with sepsis had lower bile flow (P = .001) and increased bilirubin (P = .04). Neither jejunal permeability nor bacterial translocation were different between JC, JI, or sham groups. Conclusion: Contrary to our hypothesis, the remnant anatomy does not appear to worsen the progression of IFALD. However, the role of sepsis in IFALD should be further explored, in addition to other mechanisms, including PN factors, host immune responses, and intestinal bacterial dysbiosis.     

Cranberry Proanthocyanidins Improve the Gut Mucous Layer Morphology and Function in Mice Receiving Elemental Enteral Nutrition

Background: Lamina propria Th2 cytokines, interleukin (IL)‐4 and IL‐13, stimulate goblet cell (GC) proliferation and MUC2 production, which protect the intestinal mucosa. Elemental enteral nutrition (EEN) reduces tissue IL‐4 and impairs barrier function. Proanthocyanidins (PACs) stimulate oral mucin levels. We hypothesized that adding PAC to EEN would maintain Th2–without stimulating Th1–cytokines and preserve luminal MUC2 vs EEN alone. Materials and Methods: Seventy mice were randomized to 5 diet groups–standard chow, intragastric EEN, or EEN with lowPAC, midPAC (50 mg), or highPAC (100 mg PAC/kg BW)–for 5 days, starting 2 days after gastric cannulation. Ileal tissue was analyzed for histomorphology and the cytokines IL‐4, IL‐13, IL‐1β, IL‐6, and TNF‐α by enzyme‐linked immunosorbent assay. MUC2 was measured in intestinal washes. Results: EEN lowered IL‐13 (P < .05) compared with standard chow, whereas IL‐4 was not significant (P < .07). LowPAC and midPAC increased IL‐13 (P < .05), whereas highPAC increased both IL‐4 and IL‐13 (P < .05) compared with EEN. All EEN diets reduced (P < .05) crypt depth compared with the chow group. Compared with standard chow, GC numbers and luminal MUC2 were reduced with EEN (P < .05). These effects were attenuated (P < .05) with midPAC and highPAC. No changes were observed in tissue Th1 cytokines. Conclusions: Adding PACs to EEN reverses impaired intestinal barrier function following EEN by improving the gut mucous layer and function through increased GC size and number as well as levels of MUC2 and ileal IL‐4 and IL‐13.     

Nutrition Status and Intestinal Permeability in Patients Eligible for Liver Transplantation

Background: Increased intestinal permeability has been reported in multiple studies of cirrhotic patients, although specific factors associated with this finding have not been fully elucidated. Thus, the aim of this study was to investigate whether there was an association between nutrition status measured by different methods and intestinal permeability in cirrhotic patients who were candidates for liver transplantation. Materials and Methods: The study group comprised 18 cirrhotic patients and 15 healthy controls. Patients' nutrition status was evaluated by Subjective Global Assessment (SGA), anthropometry, dynamometry, and phase angle, which was determined by bioelectrical impedance analysis. Intestinal permeability was assessed by the lactulose/mannitol test. Results: The prevalence of malnutrition showed wide variance between different assessment methods (5.5%–77.8%). Intestinal permeability was significantly higher in cirrhotic patients than in healthy controls. In relation to nutrition status, intestinal permeability and phase angle did not differ significantly between patients who were considered well nourished (median intestinal permeability, 0.010 [range, 0.001–0.198]; median phase angle, 6.0 [range, 4.2–6.9]) and malnourished patients (intestinal permeability, 0.032 [range, 0.002–0.079]; phase angle, 4.8 [range, 2.2–6.1]) by SGA. In addition, no correlation was found between nutrition diagnosis as assessed by different methods, patient age, liver disease severity scores, and laboratory measurements with intestinal permeability. Conclusion: Although intestinal permeability was increased in cirrhotic patients, this finding was not associated with nutrition status.     

Oral Citrulline Mitigates Inflammation and Jejunal Damage via the Inactivation of Neuronal Nitric Oxide Synthase and Nuclear Factor–κB in Intestinal Ischemia and Reperfusion

Background: Intestinal ischemia and reperfusion (I/R) is a life‐threatening emergency accompanied by inflammation and organ damage. We compared the mechanisms and the effects of arginine, citrulline, and glutamine on inflammation and intestinal damage. Materials and Methods: Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion and either 3 (I/R3) or 24 (I/R24) hours of reperfusion and were orally administered vehicle, arginine, citrulline, or glutamine 15 minutes before reperfusion and at 3, 9, and 21 hours of reperfusion. Results: I/R3 rats experienced jejunal damage and apoptosis, and I/R24 rats had liver dysfunction compared with normal rats (one‐way ANOVA, P < .05). Arginine and citrulline administrations improved jejunal morphology, and citrulline and glutamine administrations alleviated the loss of jejunal mass in I/R3 rats. I/R3‐increased circulating nitrate/nitrite (NOx), tumor necrosis factor–α, and interleukin‐6 were significantly decreased by citrulline, glutamine and citrulline, and arginine, glutamine, and citrulline, respectively. These amino acids decreased plasma NOx and interferon‐γ in I/R24, decreased jejunal neuronal nitric oxide synthase (NOS) protein in I/R3 rats, and alleviated jejunal apoptosis in I/R3 and I/R24 rats. In addition, the jejunal phosphorylated to total nuclear factor–κB (NF‐κB) ratio was decreased by arginine and citrulline in I/R24 rats. Conclusion: Oral administration of arginine, citrulline, and glutamine may alleviate systemic inflammation, jejunal apoptosis, and neuronal NOS in intestinal I/R. Citrulline may further attenuate jejunal damage by preserving jejunal mass, partially via the inactivation of NOS and the NF‐κB pathway. In conclusion, oral citrulline may have more benefits than arginine and glutamine in mitigating intestinal ischemia and reperfusion‐induced adverse effects.