Inducible nitric oxide synthase knockout mice are resistant to diet-induced loss of gut barrier function and intestinal injury

Loss of gut barrier function has been documented to occur in animals receiving total parenteral nutrition (TPN) and certain liquid diets. However, the mechanisms responsible for diet-induced gut barrier dysfunction remain to be fully determined. Thus we tested the hypothesis that increased intestinal nitric oxide production contributes to this phenomenon. To test this hypothesis, iNO S-deficient (iNOS -/-) mice and their wild-type littermates (iNOS +/+) were fed either chow or TPN solution for 14 days. Subsequently they were killed and gut barrier function was assessed by measuring bacterial translocation to the mesenteric lymph node (MLN) complex. Additionally, intestinal bacterial population levels, gut morphology, plasma and intestinal nitric oxide levels, as well as intestinal levels of the nitric oxide synthase (NOS) enzymes cNOS and iNOS, were measured. Bacterial translocation occurred in the iNOS +/+ but not the iNOS -/- mice receiving oral TPN solution. Oral TPN-induced bacterial translocation was associated with increased intestinal bacterial population levels as well as morphologic evidence of intestinal injury. Plasma and intestinal levels of the nitric oxide products, nitrite/nitrate, were increased in the iNOS +/+ mice fed the TPN solution but not in the chow-fed groups or the iNOS -/- mice receiving TPN solution. Last, intestinal iNOS, but not cNOS, activity was increased in the iNOS +/+ oral TPN-fed mice. These results implicate a role for increased intestinal nitric oxide production, through iNOS, in the pathogenesis of oral TPN-induced gut barrier dysfunction and injury.     

Total parenteral nutrition-induced changes in gut mucosal function: atrophy alone is not the issue.

BACKGROUND. Total parenteral nutrition (TPN) has been implicated in gut atrophy and breakdown of barrier function leading to bacterial translocation (BT) in animals. BT during TPN, however, is not found consistently, and it has therefore been suggested that macromolecular permeability may occur independently of BT during TPN. METHODS. Male Sprague-Dawley rats were administered isocaloric standard TPN enterally, parenterally, or split equally between the two routes or allowed food ad lib. A second group of rats was administered isocaloric TPN with and without 4% lipids, and changes in gut barrier function were assessed by measuring lactulose permeability. RESULTS. Rats receiving TPN both enterally and parenterally maintained histologic intestinal structure to the same degree as rats fed enterally and those allowed food. Although parenteral feeding led to significant gut atrophy and cecal bacterial overgrowth, BT was not increased. Gut permeability to lactulose, however, was increased significantly in the TPN groups. Lipid content did not affect outcome. CONCLUSIONS. These results suggest that gut atrophy, BT, and permeability to macromolecules are not necessarily related. Gut-origin septic states during TPN or trauma may be caused by an increased escape of macromolecules from the gut, and BT may be an end result rather than a primary cause of such septic episodes.     

Intravenous glutamine or short-chain fatty acids reduce central venous catheter infection in a model of total parenteral nutrition

BACKGROUND/PURPOSE: In children receiving total parenteral nutrition (TPN) translocated enteric organisms are a possible cause of central venous catheter infection. The aim of this study was to determine the relationship between gut mucosal atrophy, bacterial translocation, and catheter sepsis in rats receiving TPN alone or supplemented with intravenous short chain fatty acids (SCFA) or glutamine. METHODS: Mature Wistar rats were studied. Groups 2 to 5 had a central venous catheter inserted. Group 1 (n = 12) had enteral feeds only, group 2 (n = 14) had enteral feeds and intravenous saline, group 3 (n = 15) had TPN only, group 4 (n = 13) had TPN with SCFA, and group 5 (n = 15) had TPN with glutamine. At 1 week, blood, tissue, and catheter specimens were obtained for culture and mucosal morphometry. RESULTS: Villus height and crypt depth were reduced significantly in group 3 compared with group 1 (P < .05). Glutamine and SCFA significantly ameliorated the mucosal atrophy. Significant bacterial translocation and catheter infection occurred in group 3. Reduced translocation with SCFA was not significant, but catheter infection was (P < .05). Glutamine significantly reduced translocation and catheter infection. CONCLUSIONS: There is an association between bacterial translocation and central venous catheter infection. The risk of catheter infection is reduced by supplementing TPN with SCFA or glutamine.     

The effect of E coli virulence on bacterial translocation and systemic sepsis in the neonatal rabbit model

In the surgical neonate, three factors that promote bacterial translocation and systemic infection are: (1) intestinal bacterial colonization and overgrowth; (2) compromised host defenses; and (3) disruption of the mucosal epithelial barrier. The newborn rabbit provides an excellent model to study these factors. Like the human, there is early closure of the gut mucosa to macromolecules, and nutrition can be maintained by breast or formula feeding. This study examines translocation and systemic sepsis after colonization with virulent K1 and avirulent K100 strains of Escherichia coli. New Zealand white rabbit pups (2 to 5 days old) were studied. The gastrointestinal tracts of 12 were colonized with K1 E coli; 14 were colonized with K100 E coli; 12 control animals were not inoculated. Mesenteric lymph node (MLN), liver, spleen, and colon homogenate were cultured 72 hours postinoculation. No bacteria were isolated from the colons of all but one control animal. Translocation or systemic sepsis did not occur. Translocation to the MLN was significantly increased (P less than .03) in K1 (50%) and K100 (36%) groups compared with controls (0%). Translocation to liver and spleen (systemic sepsis) was significantly increased (P less than .03) in K1 animals (67%) compared with K100 (0%) or controls (0%). Colonization by both strains of E coli led to translocation to the MLN, but only K1 E coli caused systemic sepsis. This suggests that although colonization by E coli in the newborn leads to translocation to the MLN, progression to systemic sepsis is the result of characteristics of the bacteria and/or neonatal host responses.     

Glutamine stabilizes intestinal permeability and reduces pancreatic infection in acute experimental pancreatitis

Intestinal barrier failure and subsequent translocation of bacteria from the gut play a decisive role in the development of systemic infections in severe acute pancreatitis. Glutamine (GLN) has been shown to stabilize gut barrier function and to reduce bacterial translocation in various experimental settings. The aim of this study was to evaluate whether GLN reduces gut permeability and bacterial infection in a model of acute necrotizing pancreatitis. Acute necrotizing pancreatitis was induced in 50 rats under sterile conditions by intraductal infusion of glycodeoxycholic acid and intravenous infusion of cerulein. Six hours after the induction of pancreatitis, animals were randomly assigned to one of two groups: standard total parental nutrition (TPN) or TPN combined with GLN (0.5 g/kg⁻¹/day⁻¹). After 96 hours, the animals were killed. The pancreas was prepared for bacteriologic examination, and the ascending colon was mounted in a Ussing chamber for determination of transmucosal resistance and mannitol flux as indicators of intestinal permeability. Transmucosal resistance was 31% higher in the animals treated with GLN-supplemented TPN compared to the animals given standard TPN. Mannitol flux through the epithelium was decreased by 40%. The prevalence of pancreatic infections was 33% in animals given GLN-enriched TPN as compared to 86% in animals receiving standard TPN (P < 0.05). Adding GLN to standard TPN not only reduces the permeability of the colon but decreases pancreatic infections in acute necrotizing pancreatitis in the rat. This confirms previous reports that GLN decreases bacterial translocation by stabilizing the intestinal mucosal barrier. The present findings provide the first evidence suggesting that stabilizing the intestinal barrier can reduce the prevalence of pancreatic infection in acute pancreatitis and that GLN may be useful in preventing septic complications in clinical pancreatitis.     

Effect of stress and trauma on bacterial translocation from the gut

Previously, we established that bacteria contained within the gut can cross the GI mucosal barrier and spread systemically, a process termed bacterial translocation. Three models were used to extend this work: cold exposure (up to 16 hr at 4 degrees C), a nontissue injury stress model; femoral fracture-amputation, a trauma model; and thermal injury (30% third-degree burn), a trauma model with retained necrotic tissue. CD-1 mice either with a normal GI microflora or who were monoassociated with Escherichia coli C-25 were subjected to sham or actual stress or trauma. The animals were sacrificed at various times postinsult and the ceca, mesenteric lymph nodes (MLN), spleens, and livers were quantitatively cultured. Neither the incidence nor the magnitude of bacterial translocation was increased in the cold-exposed animals compared to control mice. The incidence of bacterial translocation to the systemic organs was higher in the animals with a normal flora receiving femoral fracture amputation (11%) (P less than 0.02) than in animals receiving a thermal injury (1%) or sham-injured control mice (0%). In contrast, the incidence of translocation to the liver or spleen was higher in burned mice monoassociated with E. coli C-25 (60%) (P less than 0.01) than in E. coli monoassociated mice sustaining femoral fracture amputation (17%). Stress alone (cold exposure) does not promote bacterial translocation; however, trauma, especially in combination with retained necrotic tissue, promotes bacterial translocation. Thus bacteria colonizing the gut can invade systemic organs after trauma, especially when the normal ecology of the gut flora has been disrupted.     

Incidence of bacterial translocation in four different models of experimental short bowel syndrome

The outcome of patients with short bowel syndrome is influenced for factors such as the length of remnant intestine or the presence or absence of ileocecal valve (ICV). Gram-negative sepsis, the main cause of mortality in this group of children, is probably due to bacterial translocation (BT), because after gut resection there are a number of circumstances that favour its occurrence, being the most known intestinal dismotility, bacterial overgrowth, loss of gut-associated lymphoid tissue, total parenteral nutrition (TPN) and fasting related mucosal atrophy. The aim of this experimental controlled study was to test the incidence of BT after four different types of gut resection, in animals fed orally or receiving TPN. Hundred and three adult Wistar rats bred and raised in our facilities according to European Union Regulations were randomly divided in six groups:--Group 1 (n = 26): non-manipulated animals, served as a control.--Group 2 (n = 14): 80% non-lethal small bowel resection, fed orally.--Group 3 (n = 15): same resection as group 2 but including ICV. Rat chow ad libitum.--Group 4 (n = 27): non-resected fasting animals receiving all-in-one TPN solution.--Group 5 (n = 11): same resection as group 2, but fasting and receiving TPN--Group 6 (n = 10): 90% small bowel resection, including cecum and ICV, fasting and TPN. The animals were maintained for 10 days in individual metabolic cages, and, at the end of the experiment, were bled by portal and cardiac puncture. Mesenteric lymph nodes, peripheral and portal blood samples were cultured for BT. Non-manipulated rats (group 1) had lower BT incidence (8%) than resected ones (groups 2, 3, 5 and 6, 93%, 60%, 91%, 60%, p < 0.05) or animals non-resected, receiving TPN (group 4.51%, p < 0.05). When resection included ICV in orally fed rats BT index was also lower (group 3 vs group 2.60% vs 91%, p < 0.05). In TPN resected animals a drop was also found in BT when ICV and cecum were added to small bowel resection (group 6 vs group 5.60% vs 91%, p < 0.05). In conclusion: 1. Gut resection is associated to a high degree of BT, even if the animals are fed orally. 2. Resection including ICV, produced less BT. 3. TPN-related BT was shown in half of the animals non resected. 4. TPN-resected rats had also less BT when ICV and cecum were removed.     

Endotoxin but not malnutrition promotes bacterial translocation of the gut flora in burned mice

Previously we have shown that under certain conditions, bacteria can pass through the intact epithelial mucosa to the mesenteric lymph nodes (MLN), liver, spleen, and bloodstream to cause infection, a process termed bacterial translocation. To extend these studies, we determined the influence of protein malnutrition and endotoxemia on bacterial translocation in burned (25% TBSA) and unburned mice. The results of these experiments documented that protein malnutrition did not promote bacterial translocation from the gut in either burned or unburned animals, although it did disrupt the normal indigenous gut flora. In contrast, a nonlethal dose of endotoxin (IP) promoted bacterial translocation to the mesenteric lymph nodes in burned and unburned mice, but only in burned mice did the bacteria translocate from the gut to other systemic organs (p less than 0.01). Furthermore, the mortality rate of mice receiving only endotoxin or burn was less than 10%, while the combination of endotoxin plus a thermal injury increased the mortality rate to 100% (p less than 0.01). These studies support the concept that bacteria may translocate from the gut to other organs and be a potential source of lethal infections after thermal injury.     

Endotoxin promotes the translocation of bacteria from the gut

Experiments were performed in mice to determine whether endotoxin could cause bacteria normally colonizing the gut to spread systemically, a process termed bacterial translocation. Endotoxin given intraperitoneally promoted bacterial translocation in a dose-dependent fashion from the gut to the mesenteric lymph node (MLN). The incidence of bacterial translocation to the MLN was similar whether the endotoxin was administered intramuscularly or intraperitoneally, although the number of bacteria colonizing the MLN was greater with intraperitoneal endotoxin. The incidence and magnitude of endotoxin-induced bacterial translocation were similar between CD-1 and C3H/HeJ (endotoxin-resistant) mice, indicating that bacterial translocation is not prevented by genetic resistance to endotoxin. Thus, it appears that the gut may serve as a reservoir for bacteria causing systemic infections during endotoxemia.     

不同营养方式对肠道缺血再灌注大鼠肠屏障功能的影响

目的探讨不同营养物质及支持途径对肠道缺血再灌注大鼠肠屏障功能和细菌易位的影响。方法60只雄性SD大鼠建立肠道缺血再灌注模型,随机分成普通肠外营养组(PN),富含谷氨酰胺的肠外营养组(G-PN),普通肠内营养组(EN)及免疫增强型肠内营养组(IEN)。从术后第1天起连续营养支持7d,各组等氮、等热卡。观察肠道形态学、肠道黏膜通透性、肠道细菌易位情况和血浆内毒素水平及肠道免疫功能检测。结果PN组肠黏膜明显萎缩,其绒毛高度、黏膜厚度、隐窝深度及绒毛表面积均显著低于其他各组(P<0.05);其肠黏膜通透性及内毒素值显著高于其他各组(P<0.05),细菌易位率(100%)明显高于其他各组(G-PN组60.0%,EN组33.3%,IEN组20.0%)。PN组CD4 T淋巴细胞和IgA 浆细胞分布显著低于其他各组(P<0.01)。结论EN在维护肠黏膜屏障功能、防止细菌及内毒素易位方面优于PN。免疫增强型EN在维护肠黏膜屏障、改善肠道免疫功能、防止细菌易位方面作用优于普通EN。     

The effect of glutamine-enriched TPN on gut immune cellularity.

Prolonged parenteral feeding with standard nutrient solutions results in significant alteration in the structural, hormonal, and immunological composition of the intestinal tract. The purpose of the following study was to evaluate the effect of glutamine-supplemented parenteral nutrition on the immune cellularity of the gut. Twenty-one Fischer rats were randomized to three groups of seven animals each. Group I was fed rat chow and water ad lib, Group II was fed a standard solution of total parenteral nutrition (TPN) (D25/4.25% amino acids) via a central venous catheter, and Group III was fed the standard solution of TPN with 2% glutamine which was isonitrogenous and isocaloric to Group II. Animals were fed their respective diets for 1 week and bile was collected and assayed for secretory IgA (s-IgA) and IgM. The terminal ileum was stained and assayed for IgA+, IgM+, IgG+, CD4+, and CD8+ plasma cells and lymphocytes. Results indicate that the feeding of a standard parenteral diet results in a significant decrease in biliary s-IgA and IgA+ plasma cells in the gut lamina propria compared to chow-fed animals (S-IgA: chow, 858 +/- 23 micrograms/ml; TPN, 494 +/- 41 micrograms/ml; IgA cells: chow, 35.7 +/- 1.8; TPN, 8.6 +/- 0.9 cells/hpf). In addition a marked depletion of CD4+ and CD8+ lymphocytes was observed with standard solutions of parenteral nutrition compared to chow (CD4+: chow, 36.8 +/- 6.6; TPN, 14.9 +/- 6.0; CD8+: chow, 18.8 +/- 5.6; TPN, 5.7 +/- 2.7 cells/hpf). The addition of glutamine to the standard TPN solution maintained both B and T cell populations at levels similar to chow-fed animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Bacterial translocation after cirrhotic liver resection: a clinical investigation of 181 patients

BACKGROUND: Cirrhotic patients are usually associated with a high susceptibility to infection. Although bacterial translocation from gut mucosa to mesenteric lymph node (MLN) and systemic circulation is a well-known phenomenon after hepatectomy, its role in cirrhotic patients remains unclear. MATERIALS AND METHODS: MLN was harvested for bacterial culture before and after liver resection in 181 cirrhotic patients. The characteristics and postoperative courses of patients with positive and negative bacterial culture for MLN after hepatectomy were compared. Postoperative systemic antibiotics were administered if infectious complications occurred. RESULTS: No bacteria were cultured in MLN before hepatectomy. Bacterial translocation (BT) to MLN after hepatectomy occurred in 36 patients (BT group). After multivariate analysis, intraoperative blood transfusion was the only independent factor that influenced bacterial translocation rates after cirrhotic liver resection. BT group patients also had higher infectious and overall complication rates, with a longer postoperative hospital stay. Among the cultured bacteriae from infected sites in BT group patients with infectious complications, only 2 patients (12.5%) had totally different bacterial species to those cultured from MLNs. CONCLUSIONS: Bacterial translocation more often occurred after liver resection in cirrhotic patients who received intraoperative blood transfusion. Such patients had higher postoperative infectious and overall complication rates. Thus, avoidance of intraoperative blood transfusion is mandatory for cirrhotic liver resection.     

Impairment of pulmonary macrophage function with total parenteral nutrition.

OBJECTIVE: The effects of total parenteral nutrition (TPN) administration on pulmonary macrophage function and host response to gram-negative pulmonary infection were evaluated. SUMMARY BACKGROUND DATA: Administration of TPN resulted in increased infectious complications in traumatized and perioperative patients, but underlying mechanisms are unclear. METHODS: Twenty-six male Wistar rats underwent central vein cannulation and were randomized to isocaloric feeding of a regular chow diet (RD) plus saline infusion or TPN without chow diet for 7 days. Pulmonary alveolar macrophage (PAM phi) superoxide production, Candida albicans phagocytosis and killing, and tumor necrosis factor (TNF) production in response to endotoxin (LPS) were assessed. Mesenteric lymph nodes (MLN) were cultured. A second group of rats (n = 6/group) were inoculated intratracheally with a sublethal dose of 9 x 10(9) live Escherichia coli per animal, and the lungs were cultured quantitatively 72 hours later to assess bacterial clearance. Finally, 11 RD-fed rats and 13 TPN-fed rats received intratracheal inoculation of 1.4 x 10(10) live E. coli and were included in follow-up. RESULTS: Administration of TPN was associated with a significant increase in bacteria positive MLN compared with those in the RD group (p < 0.01). Pulmonary alveolar macrophage superoxide production, Candida albicans phagocytosis and killing, TNF production, and pulmonary clearance of bacteria were decreased significantly in TPN-fed rats compared with those fed a regular chow diet (p < 0.05). These pulmonary macrophage function changes were associated with a significantly higher mortality in TPN-fed rats compared with RD-fed rats after higher dose pulmonary E. coli inoculation. CONCLUSIONS: Defective host pulmonary antimicrobial immune responses during TPN are associated with intestinal bacterial translocation, and may explain increased infectious complications.     

Small bowel transplantation promotes bacterial overgrowth and translocation

Alterations in the symbiotic relationship between immunocompromised hosts and their resident gut microflora may lead to serious complications following small bowel transplantation (SBT). This study examined the effects of SBT and cyclosporine (CsA) immunosuppression on gut bacterial populations and translocation to the mesenteric lymph nodes. Sixty adult male meat-fed Lewis rats were divided into six groups: normal controls, CsA alone (24 mg/kg im qod), CsA carrier vehicle alone, isografts, isografts given CsA, and allografts given CsA. Rats were killed after 3 weeks and segments of small bowel and colon were harvested for quantitative tissue culture. Mesenteric lymph nodes and blood were cultured to identify translocation. Transplantation alone led to an increase in gram-negative aerobes from 2.6 to 4.6 colony forming units/100 mg tissue (P less than 0.05) in the distal ileum (transplanted segment). Eighty-four percent of transplanted animals receiving CsA had bacteria recovered from their mesenteric lymph nodes compared to none in controls (P less than 0.001) and 20% in isografts not receiving CsA (P less than 0.02). Intestinal transplantation alone appears to promote gram-negative overgrowth while the addition of CsA therapy facilitates translocation to the mesenteric lymph nodes and may predispose to gut-associated sepsis following SBT.     

Total parenteral nutrition promotes bacterial translocation from the gut

Bacterial translocation from the gut may be the primary event in many disease processes. The purpose of this study was to examine the route of nutrient administration on bacterial translocation from the gut. Each of 90 female Fischer rats underwent placement of a central venous catheter and was randomized to one of three groups. Group I (control) received food and water ad libitum. Group II received standard TPN solution orally from a bottle sipper and drank the solution ad libitum. Group III underwent TPN via the central catheter by pair feeding of the animals with group II. Animals were fed for 2 weeks, and liver, spleen, mesenteric lymph nodes, blood, and cecum were aseptically obtained for culture. A statistically significant difference (p less than 0.014) was found between translocation rates of parenterally fed animals compared with enterally fed animals. Two thirds of the animals (18/27) fed parenterally had culture-positive mesenteric lymph nodes compared with one third (9/27) of the enterally fed group and none (0/30) of the control group. A statistically significant increase in the cecal bacterial count was demonstrated in the animals fed the TPN solution, independent of route. Parenteral nutrition promotes bacterial translocation from the gut by increasing the cecal bacterial count and impairing intestinal defense.     

Cholecystokinin prophylaxis of parenteral nutrition-induced gallbladder disease.

Recent studies indicate that long-term total parenteral nutrition (TPN) induces gallstone formation and acalculous cholecystitis in humans. Cholecystectomy is hazardous for these patients because they frequently have multiple medical problems and have undergone numerous abdominal operations. The present study was designed to develop a method to prevent TPN-induced gallbladder disease. The authors tested the hypothesis that a single daily intravenous infusion of cholecystokinin-octapeptide (CCK-OP) will prevent TPN-induced gallbladder stasis. Eleven prairie dogs received TPN for 10 days. Six of these animals were given a daily infusion of CCK-OP. Control animals were fed ad lib. Each animal's bile salt pool was labeled with intravenous 3H-cholic acid 16 hours prior to acute terminal experiments. The ratio of gallbladder to hepatic bile 3H-cholic acid specific activity (Rsa) provides an index of gallbladder stasis. A Rsa of less than 1.0 indicates gallbladder stasis. TPN animals had a Rsa of 0.54 +/- 0.13 (p less than 0.01 vs. controls), indicating stasis of bile in the gallbladder. Daily CCK-OP infusions resulted in a Rsa of 0.92 +/- 0.10 (p less than 0.05 vs. TPN without CCK-OP), indicating that TPN-induced gallbladder stasis is prevented by daily CCK-OP. Control animals had a Rsa of 1.03 +/- 0.06. The cholesterol saturation indices of gallbladder and hepatic bile were not increased by TPN or CCK-OP. These data indicate that 1) TPN induces gallbladder stasis but does not increase bile lithogenic index; and 2) daily injections of CCK-OP prevent TPN-induced gallbladder stasis.     

The gut as a portal of entry for bacteremia. Role of protein malnutrition.

The current studies were performed to determine the influence of malnutrition alone or in combination with endotoxemia in promoting bacterial translocation from the gastrointestinal tract. Bacterial translocation did not occur in control, starved (up to 72 hours), or protein-malnourished (up to 21 days) mice not receiving endotoxin. Bacterial translocation to the mesenteric lymph nodes (MLNs) occurred in 80% of control mice 24 hours after receiving endotoxin (p less than 0.01). However, the combination of malnutrition plus endotoxin was associated with a higher incidence of translocation to the systemic organs (p less than 0.01), and higher numbers of bacteria per organ (p less than 0.01), than was seen in normally nourished mice receiving endotoxin. Additionally, mice that were protein malnourished were more susceptible to the lethal effects of endotoxin than were control animals, and the mortality rate was directly related to the degree of malnutrition (R2 = 0.93) (p less than 0.05). Histologically, endotoxin in combination with protein malnutrition resulted in mechanical damage to the gut mucosal barrier to bacteria. Thus, in the mice that were protein malnourished the spread of bacteria from the gut could not be controlled nor could translocated bacteria be cleared as well as normally nourished mice receiving endotoxin. These results support the concept that under certain circumstances the gut may serve as a clinically important portal of entry for bacteria.     

Acidification of formula reduces bacterial translocation and gut colonization in a neonatal rabbit model

BACKGROUND/PURPOSE: The authors hypothesized that gastric acidity is protective because it is bactericidal. They tested acidified formula for protection against gut colonization and bacterial translocation. METHODS: In vitro: Formula was acidified to pH of 2, 3, 4, 5 and innoculated with Enterobacter. Growth over time was quantitatively assessed. In vivo: 442 premature rabbit pups were sorted randomly and fed formula of pH 2, 3, 4, or 7, with ranitidine. Two models were utilized: (1) with bacterial challenge using a known acid sensitive organism, (2) without bacterial challenge to simulate natural gut colonization and to test against organisms of unknown acid sensitivity. Normal acid animals received pH 7 formula, no ranitidine. On day 3, the mesenteric lymph nodes (MLN), spleen, liver, and cecum were harvested and cultured. RESULTS: Bacterial growth was inhibited at pH 2 and 3, growth was logarithmic above pH 4 (P<.001). Total and organ-specific translocation was reduced at pH 3 and below in both models (P<.05). Translocation with formula pH 3 equaled normal acid animals. Quantitative cecal colonization was reduced in pups receiving pH 3 and below in both models (P<.05). CONCLUSION: Acidification of formula below pH 4 is bactericidal to enteric organisms. Acidified formula decreases bacterial translocation and gut colonization.     

Food without fiber promotes bacterial translocation from the gut

To determine whether the route and/or composition of nutritional support alters intestinal barrier function (measured as bacterial translocation), rats were divided into three groups: food (controls), intravenous total parenteral nutrition (IV-TPN) fed, and oral total parenteral nutrition (ORAL-TPN) fed. Bacterial translocation did not occur in the rats that were fed normally, but did occur in 60% of the rats fed the IV-TPN or the ORAL-TPN diets for 7 days (p less than 0.05). Since both the IV-TPN and ORAL-TPN diets induced bacterial translocation and the TPN solution (28% glucose and 4.5% amino acids) lacks fiber, two additional groups of rats were fed orally 2.5 gm cellulose powder/day plus TPN solution by either the intravenous or the oral route. The addition of cellulose powder decreased the incidence of bacterial translocation to 8% in the group fed the ORAL-TPN diet and to 0% in the group fed the IV-TPN diet. Cellulose improved intestinal barrier function, even though it did not prevent bacterial overgrowth or the loss of mucosal mass in the rats fed the IV-TPN or ORAL-TPN diets. Cellulose powder appears to have prevented bacterial translocation primarily by preventing IV-TPN- or ORAL-TPN-induced alterations in mucosal structure. Thus the oral administration of this fiber maintains intestinal barrier function and prevents bacterial translocation even in the absence of oral nutrients.