Elemental diet alters macrophage function in mice

Administration of a chemically defined liquid elemental diet (ED) induces spontaneous bacterial translocation to mesenteric lymph nodes (MLN) in animal models. The influence of this process on host immunity is unclear. This study evaluated the effects of ED on peritoneal macrophage (PM phi) antimicrobial functions. Conventional C57/BL6 mice and endotoxin-resistant C3H/HeJ mice (n = 60) were randomized to be pair-fed either an ED or regular chow diet (RD) for 14 days. Blood, spleen, liver, and MLN were cultured for bacteria. PM phi were harvested for: percentage Candida albicans (CA) phagocytosis, percentage killing of CA, PM phi superoxide anion (O2-) production, and TNF-dependent macrophage cytotoxicity. Enteral feeding of ED in conventional C57/BL6 mice caused significant bacterial translocation to MLN but not other organs. Significant impairment of CA killing by PM phi occurred in the ED group and was associated with reduced O2- production. Tumor necrosis factor (TNF)-dependent cytotoxicity of PM phi was also decreased. In endotoxin-resistant C3H/HeJ mice, bacterial translocation was not observed and PM phi antifungal functions remained similar in both RD and ED groups. Thus, enteral feeding of an elemental diet downregulates host oxidative and antimicrobial mechanisms and TNF-dependent cytotoxicity in conventional mice which may be secondary to elemental diet-induced bacterial translocation.     

Oral-TPN-induced bacterial translocation and impaired immune defenses are reversed by refeeding

Although certain defined diets have been shown to promote bacterial translocation (BT), the ability to reverse diet-induced BT has not previously been investigated. Furthermore, little is known about the effects of defined diets on host immune defenses. To address these questions, we measured BT and immune reactivity in rats fed a normal diet or enteral elemental (ORAL-TPN) diet. After 7 days on the elemental or normal diet, the rats were killed, and BT and mitogen responsiveness to concanavalin A and phytohemagglutinin were measured. In separate experiments, the effects of these diets on in vivo host defenses was measured with a Staphylococcus aureus abscess model. Additional experiments were performed to determine the time required to reverse ORAL-TPN-induced BT and impairment of host immune defenses by reinstituting normal feedings. Administration of the ORAL-TPN diet for 7 days was associated with BT to the mesenteric lymph node complex of all animals, decreased blastogenic response of blood and splenic lymphocytes to mitogens, and decreased ability to control an in vivo infectious challenge with S. aureus. Each of the derangements was reversed by the reinstitution of normal feedings. In summary, the enteral administration of an elemental diet for 7 days is associated with disruption of the gut microflora, BT, and the development of an immunocompromised state, all of which can be reversed by refeeding the animals a normal diet.     

Secretory immunoglobulin A, intestinal mucin, and mucosal permeability in nutritionally induced bacterial translocation in rats.

OBJECTIVE. The authors investigated the role of mucin and secretory immunoglobulin A (slgA) in a model of nutritionally induced bacterial translocation. BACKGROUND. Parenteral and certain elemental diets have been shown to impair intestinal barrier function, whereas fiber has been shown to protect against nutritionally induced bacterial translocation. However, the factors responsible for these phenomenon have not been fully determined. METHODS. Intestinal mucin levels, mucosal protein content, slgA, intestinal morphology, and permeability to horseradish peroxidase, bacterial translocation, and intestinal bacterial population levels were measured in rats 7 days after receiving total parenteral nutrition (TPN) solution (28% glucose, 4.25% amino acids; 307 kcal/kg/day) enterally (ORAL-TPN) or parenterally (IV-TPN) with or without enteral bulk fiber supplementation. Chow-fed rats served as control subjects. RESULTS. The incidence of bacterial translocation in the ORAL-TPN and IV-TPN groups was reduced significantly by the provision of fiber (p < 0.05). Mucosal protein, slgA, and insoluble mucin levels were decreased in the jejunum of the ORAL-TPN and IV-TPN groups, with mucosal protein levels being decreased to a greater extent than slgA or mucin. Although similar decreases in these parameters were observed in the fiber-fed groups, fiber appeared to improve intestinal barrier function as measured by horseradish peroxidase permeability. CONCLUSIONS. The provision of bulk-forming fiber improves intestinal barrier function as measured by peroxidase permeability and bacterial translocation, but does not restore mucosal protein content, intestinal mucin, or slgA levels to normal.     

Organ Transplantation: From Myth to Reality

Short bowel syndrome comprises the sequel of nutrient, fluid, and weight loss that occurs subsequent to greatly reduced functional surface area of the small intestine. The aim of this study is to investigate the trophic and functional effects of bombesin on remaining gut in rats with experimentally induced short bowel syndrome. Thirty-two rats were allocated randomly and experimental short bowel syndrome was induced by 80% bowel resection in all rats. A regular enteral diet and isocaloric elemental enteral nutrition for 12 days were given in the control group and the elemental nutrition group, respectively. In the bombesin group 10 μg/kg subcutaneous bombesin (tid) for 10 days with regular enteral diet for 12 days was given. In the elemental nutrition and bombesin group the diet consisted of 10 μg/kg subcutaneous bombesin (tid) for 10 days with isocaloric elemental enteral nutrition for 12 days was given. All rats underwent physical, histological, and biochemical evaluation. Reduction in weight loss, bowel diameter, fecal fat content, and glycemia, increase in cellularity, and d-xylose absorption were observed in all treatment groups. These changes were more evident in the bombesin treatment groups. Increases in serum protein and albumin levels were seen with bombesin treatment with or without elemental diet, whereas reductions in villous height and crypt depth were observed only with bombesin treatment without elemental diet. Serum calcium, iron, and vitamin B₁₂levels were not affected with any treatment. It is concluded that bombesin may be a useful trophic agent contributing to increased absorptive capacity and improved biochemical values even in the absence of elemental nutrition.     

Bombesin in short bowel syndrome.

Short bowel syndrome comprises the sequel of nutrient, fluid, and weight loss that occurs subsequent to greatly reduced functional surface area of the small intestine. The aim of this study is to investigate the trophic and functional effects of bombesin on remaining gut in rats with experimentally induced short bowel syndrome. Thirty-two rats were allocated randomly and experimental short bowel syndrome was induced by 80% bowel resection in all rats. A regular enteral diet and isocaloric elemental enteral nutrition for 12 days were given in the control group and the elemental nutrition group, respectively. In the bombesin group 10 microg/kg subcutaneous bombesin (t.i.d.) for 10 days with regular enteral diet for 12 days was given. In the elemental nutrition and bombesin group the diet consisted of 10 microg/kg subcutaneous bombesin (t.i.d.) for 10 days with isocaloric elemental enteral nutrition for 12 days was given. All rats underwent physical, histological, and biochemical evaluation. Reduction in weight loss, bowel diameter, fecal fat content, and glycemia, increase in cellularity, and d-xylose absorption were observed in all treatment groups. These changes were more evident in the bombesin treatment groups. Increases in serum protein and albumin levels were seen with bombesin treatment with or without elemental diet, whereas reductions in villous height and crypt depth were observed only with bombesin treatment without elemental diet. Serum calcium, iron, and vitamin B(12) levels were not affected with any treatment. It is concluded that bombesin may be a useful trophic agent contributing to increased absorptive capacity and improved biochemical values even in the absence of elemental nutrition.     

Bombesin improves survival from methotrexate-induced enterocolitis.

OBJECTIVE: The authors determined whether bombesin could improve survival from methotrexate (MTX)-induced enterocolitis. SUMMARY BACKGROUND DATA: Bombesin prevents gut mucosal atrophy, which is produced by feeding rats an elemental diet. Administration of MTX produces a lethal enterocolitis in rats fed an elemental diet. METHODS: On treatment day 0, 60 rats were divided randomly into three groups and fed an elemental diet (Vivonex TEN, Sandoz, Minneapolis, MN) as the only source of nutrition. Groups were subdivided further to receive either saline or bombesin (10 micrograms/kg, subcutaneously, three times a day) beginning either on day 0 or day 14. Methotrexate (20 mg/kg, intraperitoneally) was given to all rats 14 days after the start of an elemental diet. RESULTS: Bombesin prevented the mucosal atrophy in the ileum produced by the elemental diet and significantly decreased mortality in rats given MTX (whether given as a pretreatment or at the time of MTX administration). CONCLUSION: Bombesin significantly improved survival in a lethal model of MTX-induced enterocolitis, possibly by maintaining gut mucosal structure. Administration of bombesin to patients receiving chemotherapy may be clinically useful in preventing the severe enterocolitis induced by various chemotherapeutic agents.     

Hemorrhagic shock-induced bacterial translocation is reduced by xanthine oxidase inhibition or inactivation

Experiments were performed to determine whether bacterial translocation (BT) after hemorrhagic shock is due to a reperfusion injury mediated by xanthine oxidase-derived oxidants. Rats were subjected to 30 minutes of shock (30 mm Hg) followed by reinfusion of shed blood. Twenty-four hours after hemorrhage and reinfusion, the mesenteric lymph node, liver, and spleen were harvested from each animal for bacterial culture, and the ileum and cecum were examined histologically. Sham-shocked (control) rats were instrumented, but blood was not withdrawn. The incidence of BT was higher in the shocked rats (61%) than in the sham-shocked animals (7%) (p less than 0.01). Allopurinol (50 mg/kg, administered orally), a competitive inhibitor of xanthine oxidase, reduced the incidence of shock-induced BT to 14% (p = 0.02). Similarly, rats fed a tungsten-supplemented molybdenum-free diet, which inactivates xanthine oxidase, reduced shock-induced BT to 10% (p = 0.02). The histologic damage cause by hemorrhagic shock was prevented by blocking xanthine oxidase activity. Thus hemorrhagic shock-induced bacterial translocation from the gut appears to be mediated by oxidants generated by activation of the xanthine oxidase system.     

Splenectomy influences endotoxin-induced bacterial translocation

To determine whether splenectomy affects the antibacterial defenses of the gut, experiments were performed using bacterial translocation (BT) as a marker of intestinal barrier failure. The incidence of BT was measured 8 days after splenectomy or sham-splenectomy in mice receiving or not receiving endotoxin (0.1 mg IP). Splenectomy does not appear to promote BT from the gut, since the incidence of bacterial translocation after splenectomy or sham-splenectomy (5%) were not different. A second experiment was performed to determine whether the resistance to endotoxin-induced BT was modified after splenectomy. The incidence of endotoxin-induced BT was 73% in the unoperated control group, 59% in the sham-splenectomy group, but 23% in the splenectomy group (p less than 0.002). Thus, splenectomy but not sham-splenectomy increased the resistance of otherwise healthy mice to endotoxin-induced BT.     

Elemental diet and IV-TPN-induced bacterial translocation is associated with loss of intestinal mucosal barrier function against bacteria.

OBJECTIVE: The goal of the current study was to directly assess the role of loss of mucosal barrier function in nutritionally induced bacterial translocation. BACKGROUND: Parenteral and certain elemental enteral diets have been shown to promote bacterial translocation. The mechanisms underlying this observation, especially the question of whether nutritionally induced bacterial translocation is primarily related to loss of intestinal barrier function, versus an impaired immune system, remain to be fully elucidated. METHODS: Bacterial translocation was measured in vivo, ileal mucosal membranes were harvested, and their electrophysiologic properties and barrier function were measured ex vivo in the Ussing chamber system 7 days after receiving total parenteral nutrition solution parenterally (IV-TPN) or enterally (elemental diet). Chow-fed rats served as control subjects. RESULTS: The incidence of bacterial translocation was significantly increased both to the mesenteric lymph nodes in vivo and across the in vitro Ussing chamber-mounted ileal mucosal membranes of the elemental diet-fed and IV-TPN-fed rats. The magnitude of Escherichia coli and phenol red transmucosal passage in the Ussing chamber was significantly higher in the IV-TPN-fed rats than in the elemental diet-fed or chow-fed animals. The potential differences across the ileal membrane were similar between the three groups at all time points. However, the specific resistances of the ileal membranes of the IV-TPN and elemental diet groups were significantly less than the chow-fed animals, indicating increased membrane permeability. CONCLUSIONS: Loss of intestinal barrier function plays a major role in nutritionally induced bacterial translocation, and the loss of mucosal barrier function to both E. coli and phenol red appeared greater in the IV-TPN than the elemental diet-fed rats.     

Arginine-supplemented diets improve survival in gut-derived sepsis and peritonitis by modulating bacterial clearance. The role of nitric oxide.

OBJECTIVE: The effect of arginine on survival rates and host defense mechanisms was studied using two clinically relevant models of infection that included transfusion-induced immunosuppression. SUMMARY BACKGROUND DATA: Dietary arginine will improve resistance to infection but its role in transfusion-induced immunosuppression and bacterial translocation (gut-derived sepsis) has not been defined. METHODS: Balb/c mice were fed for 10 days with either a defined AIN-76A diet, an AIN-76A diet supplemented with 2% arginine, an AIN-76A diet supplemented with 4% glycine, or standard laboratory chow. In most experiments, the mice were then transfused with allogeneic blood and allowed to feed for an additional 5 days before undergoing either cecal ligation and puncture (CLP) or gavage with 10(10) Escherichia coli and a 20% burn injury. Additional animals fed with the arginine supplemented diet were treated with the nitric oxide inhibitor N omega-Nitro-L-arginine (NNA) before gavage and burn. The effect of these diets and NNA on the degree of translocation of 14C-radiolabeled E. coli from the intestine and the ability of the host to kill translocated organisms was also investigated. Mice were fed and received transfusion, gavage, and burn as above. Mesenteric lymph nodes (MLN), liver and spleen were harvested 4 hours postburn. RESULTS: Survival after CLP was 56% in the arginine-supplemented group versus 28% in the AIN-76A group and 20% in the chow group (p < 0.02). After gavage and burn, survival was 100% in the arginine-supplemented group versus 50% in both the glycine-supplemented and chow groups and 35% in the AIN-76A group (p < 0.01). In animals receiving the arginine-supplemented diet, treatment with NNA decreased survival from 95% to 30.5% (p < 0.0001). Greater translocation, as measured by radionuclide counts, was observed to the MLN of the AIN-76A group. However, there was no difference in translocation to the liver and spleen related to dietary group. Quantitative colony counts and the calculated percentage of remaining viable bacteria showed that the ability to kill translocated organisms was significantly enhanced in animals receiving arginine. Treatment with NNA reversed the beneficial effects of arginine on immune defense. CONCLUSIONS: The benefit of arginine appears to be mediated by improved bactericidal mechanisms via the arginine-nitric oxide pathway.     

The effect of endogenous cholecystokinin released by bombesin and trypsin inhibitor on the regeneration of the pancreas.

OBJECTIVE: This study examined the effects of endogenous cholecystokinin (CCK) released by bombesin and FOY-305 (a synthetic inhibitor of trypsin on pancreatic regeneration in rats). SUMMARY BACKGROUND DATA: Trophic gut hormones (CCK and bombesin) stimulate the growth of the normal rat pancreas. However, the influence of endogenous gut hormones on pancreatic regeneration is unclear. METHODS: Male Fisher rats (n = 6 to 8 per group) were fed a protein-free diet and given ethionine (700 mg/kg intraperitoneally daily) for 8 to 9 days to induce degeneration of the pancreas. Regeneration was stimulated by giving the rats a regular chow diet. The effects of bombesin (10 micrograms/kg three times a day for 7 days) or FOY-305 (200 mg/kg daily for 8 days) on the process of regeneration were examined. RESULTS: At the end of the degeneration phase, there was near-total destruction of pancreatic acinar cells. Both bombesin and FOY-305 stimulated pancreatic regeneration. Growth measurements (weight and total content of DNA and protein) were significantly increased (p < 0.05) in the bombesin- and FOY-305-treated rats compared with controls. Histologic examination revealed widespread repopulation of the pancreas with acinar cells in the bombesin- and FOY-305-treated groups. The stimulating effects of both bombesin and FOY-305 on pancreatic regeneration were blocked completely by the CCK-receptor antagonist L-364,718. Growth measurements were not significantly increased in the groups of control rats or rats given L-364,718 alone. CONCLUSIONS: These results show that bombesin and FOY-305 significantly stimulated pancreatic regeneration. Because the stimulating effects of bombesin and FOY-305 on regeneration were blocked by the specific CCK-receptor antagonist L-364,718, it was concluded that this effect was mediated by endogenous CCK.     

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.     

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.     

Effect of different enteral nutrients on bacterial translocation in experimental obstructive jaundice

Obstructive jaundice leads to bacterial translocation (BT) by disruption of the gut barrier, intestinal microecology, and impaired host immune defence. The objective of the present study is to investigate the effects of different enteral nutrients on BT that is induced by obstructive jaundice in rats. Eighty male Wistar-Albino rats were randomly assigned into 4 groups. Group 1: 20 rats underwent laparotomy, common bile duct (CBD) was not actually ligated and transected, but sham ligation of CBD was performed. Groups 2-4: 60 rats underwent laparotomy, CBD ligation and transection. Group 1 and 2 rats were given rat chow, group 3 rats were fed a glutamine and arginine supplemented enteral diet, and group 4 rats were fed an arginine, m-RNA and omega-3 supplemented enteral diet, an immunonutrient. Rats in groups 3 and 4 had significantly less BT to mesenteric lymph nodes compared to rats in group 2 (p = 0.001). These findings suggest that oral administration of an arginine and glutamine supplemented diet and immunonutrition reduce BT in rats with obstructive jaundice.     

Effect of Probiotic Supplementation on Bacterial Translocation in Thermal Injury

Purpose To examine the effects of probiotic supplementation and enteral solutions containing glutamine and arginine on bacterial translocation (BT) and intestinal villous atrophy in thermal injury.Methods Forty male Sprague-Dawley rats weighing 200–250 g were divided into four groups of ten. Group 1 served as control group without thermal injury and was fed standard chow. Thermal injury was inflicted as a 30% scald burn in the other three groups. Group 2 was fed standard chow and group 3 was fed standard chow supplemented with a probiotic (Acidophilus plus) containing Bifidobacterium bifidum, Lactobacillus acidophilus, and Lactobacillus bulgaricus (2 × 10⁹ CFU/day) via an orogastric tube. Group 4 was fed only an enteral diet (Stresson multifiber) containing glutamine, arginine, and medium chain triglyceride, at 1 g/kg per day amino acid and 230 kcal/kg, for 7 days before thermal injury. All the animals were killed 24 h after thermal injury, and ileal segments were resected and examined histopathologically. To evaluate BT, samples from blood, mesenteric lymph nodes, and cecal content were cultured under aerobic and anaerobic conditions. Terminal ileum specimens were histologically examined to evaluate mucosal integrity.Results Significantly less BT was seen in groups 3 and 4 than in group 2 (P < 0.001). No significant difference was found between groups 3 and 4. Histological evaluation showed significant reduction in villous atrophy in groups 3 and 4.Conclusion Probiotic supplementation seems to reduce bacterial translocation and decrease intestinal mucosal atrophy in rats with thermal injury, as do enteral solutions with arginine and glutamine.     

大鼠脊髓损伤致截瘫后肠道细菌移位的实验研究

目的：探讨大鼠脊髓损伤致截瘫后是否发生肠道细菌移位。方法：建立大鼠脊髓损伤性截瘫模型，以脊髓损伤性截瘫后12h、24h、48h大白鼠为实验组，未损伤脊髓的正常大白鼠为对照组。在无菌条件下，采集动物下腔静脉血进行内毒素定量测定和细菌培养，采集肝、脾、肠系膜淋巴结、肠腔内容物作细菌培养并进行菌种鉴定。取实验组和对照组各动物的肝、脾、肠系膜淋巴结、空肠、回肠进行病理切片HE染色检查，取空、回肠进行电镜检查。结果：大鼠脊髓损伤致截瘫后24h开始出现内毒素血症，截瘫后48h出现细菌移位。结论：大鼠脊髓损伤致截瘫后将发生肠道细菌移位，提示脊髓损伤截瘫的病人应尽早给予抗生素治疗。     

Effect of probiotics on intestinal regrowth and bacterial translocation after massive small bowel resection in a rat

Background/Purpose

Because of their ability to inhibit intestinal bacterial overgrowth, probiotics (PROs) have been advocated for the treatment of patients with short bowel syndrome (SBS). This study was conducted to determine the effect of PROs on bacterial translocation and intestinal regrowth after massive small bowel resection in a rat.

Methods

Male Sprague-Dawley rats were divided into 3 experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent 75% small bowel resection, and SBS-PRO rats underwent bowel resection and were treated with a PRO given in drinking water from day 4 through 14. Intestinal structural changes (bowel circumference, overall bowel and mucosal weight, mucosal DNA and protein, villus height and crypt depth, enterocyte proliferation and enterocyte apoptosis) and bacterial translocation (BT) to mesenteric lymph nodes, liver, portal blood, and peripheral blood were determined on day 15 after operation.

Results

Sham rats exhibited a 20% BT to the mesenteric lymph nodes (level I), liver (level II), and blood (level III). Short bowel syndrome rats demonstrated a 100% BT to lymph nodes (level I) and liver (level II) and 40% translocation to peripheral blood (level III). Treatment with PROs resulted in a significant decrease in BT to all 3 target organs and decreased enterocyte apoptosis compared with SBS-untreated animals. Short bowel syndrome rats showed a significant increase (vs sham) in jejunal and ileal bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth. Short bowel syndrome rats also had a greater proliferation index and apoptotic index in both jejunum and ileum compared with sham animals. SBS-PRO rats showed a significant increase (vs SBS rats) in crypt depth in ileum and a mild decrease in apoptotic index in jejunum and ileum, compared with SBS-untreated animals.

Conclusions

In a rat model of SBS, PROs decrease BT through mechanisms which maybe dependent on intestinal mucosal integrity.     

Antibiotic prophylaxis diminishes bacterial translocation but not mortality in experimental burn wound sepsis

Pseudomonas (PSA) burn wound sepsis results in prolonged bacterial translocation (BT) of enteric organisms such as E. coli to the mesenteric lymph nodes (MLN) and organs in rats. Intestinal decontamination with oral antibiotics may improve mortality after burn injury, perhaps due to decreased BT. To determine the effect of oral antibiotic prophylaxis effective against E. coli but not PSA on BT and subsequent mortality in a model of PSA burn wound sepsis, rats were given a 30% scald burn and wound inoculation with 10(8) PSA followed by randomization to either ampicillin (50 mg/kg/d) or saline gavage. Cultures of MLN, organs, blood, and cecal contents were obtained on days 1, 4, and 7 after injury, with additional animals observed for 14-day mortality. Although oral antibiotic prophylaxis resulted in increased cecal colony counts, the incidence of BT was unchanged. The number of organisms present in both the MLN and organs, however, was significantly reduced with prophylaxis, indicating cecal overgrowth by non-translocating bacteria. Reduction of the number of translocating organisms did not result in improved mean survival time after injury, suggesting that mortality from PSA burn wound sepsis occurs independently of bacterial translocation.     

Role of bombesin on gut mucosal growth.

OBJECTIVE: The authors examined the effects of exogenous bombesin (BBS) on gut mucosal growth in chow-fed rats and the mucosal regeneration after gut atrophy brought about by feeding an elemental diet and after intestinal injury produced by methotrexate (MTX). SUMMARY BACKGROUND DATA: Bombesin is one of many gastrointestinal peptides implicated in the regulation of gut mucosal growth. Although BBS is known to stimulate growth of normal pancreatic tissue, the trophic effect of BBS on gut mucosa is less clear and its exact role in gut mucosal regeneration and repair is not known. METHODS: Rats were fed a regular chow diet (control) or an elemental diet plus either saline or BBS (10 micrograms/kg). In another experiment, rats fed a chow diet and treated with saline or BBS were given MTX (20 micrograms/kg) or a single intraperitoneal injection. In all experiments, small and large bowel mucosa and pancreas were removed and analyzed for BBS-mediated proliferation. RESULTS: Bombesin produced significant mucosal proliferation of the small bowel at day 14, but not at day 7, in rats fed regular chow. In contrast, BBS treatment for 7 days produced significant proliferation in both the atrophic and injured gut mucosa of rats given elemental diet or MTX. CONCLUSIONS: Bombesin may be an important enterotrophic factor for normal mucosal proliferation and may be clinically beneficial as an agent to restore or maintain gut mucosa during periods of atrophy or injury.     

Bacterial overgrowth and intestinal atrophy in the etiology of gut barrier failure in the rat

Bacterial translocation occurs in animal models of shock, trauma, sepsis, and parenteral or elemental enteral alimentation. Bowel atrophy and cecal bacterial overgrowth have both been implicated in the pathophysiology of bacterial translocation in many of these models. To further define the etiology of bacterial translocation resulting from dietary manipulations, rats were fed a elemental/defined-formula diet (DFD) for 2 weeks ad libitum and then randomized to either intestinal decontamination with a nonabsorbable antibiotic (neomycin) or no antibiotic treatment. Neomycin treatment significantly (p less than 0.01) reduced the incidence of bacterial translocation after DFD, in association with a significant reduction in the number of cecal gram-negative bacteria. Neither loss of bowel mass after DFD nor bowel composition was affected by oral neomycin. Bacterial translocation after DFD would thus appear to be the result of cecal bacterial overgrowth rather than a loss of a physical intestinal barrier due to atrophy.