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.     

Probiotic supplementation reduces the risk of bacterial translocation in experimental short bowel syndrome

Background/Purpose: Probiotics are live organisms that survive passage through the gastrointestinal tract and have beneficial effects on the host. Lactobacillus and Bifidobacterium have been recommended for cholesterol lowering, acute diarrhea, prevention of cancer, or inflammatory bowel disease. On the other hand, after massive bowel resection, bacterial overgrowth is frequent and favors bacterial translocation (BT). The possible beneficial effects of Bifidobacterium lactis (BL) administration on BT in experimental short bowel syndrome (SBS), have not been investigated. The aim of this study was to test the hypothesis that BL administration decreases BT in SBS in animals fed orally. Methods: One hundred twenty-eight adult Wistar rats fed orally with standard rat chow and tap water [ldquo ]ad libitum[rdquo ] were maintained in individual metabolic cages for 10 days and divided into 3 groups: control group (n = 71): nonmanipulated animals; RES group (n = 39): 80% gut resection from 10 cm beyond the angle of Treitz to 10 cm above the cecum; RES-PRO group (n = 18): same resection and daily 7.8 [times ] 10⁸ CFU B Lactis administration, after orogastric intubation. At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood specimens were recovered and cultured. Bacterial identification in blood was made by conventional methods, and MLN culture was considered positive with a growth over 100 CFU/g. Results: Bacterial translocation was detected in 6% of control group rats. The incidence of BT in the RES group was 87% (34 of 39), whereas only 50% (9 of 18) of RES-PRO animals had BT (P [lt ] .05). The relative risk reduction (RRR) was 0.43 (95% Cl 0.14 to 0.72), and the number needed to treat (NNT) was 3 (95% Cl 2 to 8). In other words, animals that received BL had the risk of BT reduced by 43% (RRR of 0.43), and of every 3 animals treated, 1 is expected to be free of BT (NNT of 3). Conclusion: Administration of B Lactis reduces the incidence of BT in adult Wistar rats after 80% gut resection.     

Effect of growth hormone, epidermal growth factor, and insulin on bacterial translocation in experimental short bowel syndrome

BACKGROUND/PURPOSE: An adaptive process starts in the remaining intestine after massive resection, and several trophic factors including growth hormone (GH), epidermal growth factor (EGF), and insulin (INS) have been shown to have a positive effect on it. Bacterial translocation (BT) is frequent after extensive small bowel resection, but the effects of GH, EGF, or INS have not been investigated in experimental short bowel syndrome (SBS). This study tests the hypothesis that GH, EGF, or INS decrease BT in SBS in rats with parenteral nutrition (PN). METHODS: Thirty-eight adult Wistar rats underwent central venous cannulation and were assigned randomly to 1 of 4 groups receiving for 10 days 4 treatment regimes: (1) PN group (n = 10): fasting, all-in-one PN solution (300 mL/kg/24 h, 280 kcal/kg/24 h), 80% gut resection including ileo-cecal valve; (2) GH group (n = 9): fasting, same PN regime and resection, GH (1 mg/kg/d, subcutaneously); (3) EGF group (n = 9): fasting, PN, resection, EGF (150 microg/24 h intravenously); (4) INS group (n = 9): fasting, PN, resection, INS (1 UI/100 g/24 h subcutaneously). At the end of the experiment they were killed, and mesenteric lymph nodes (MLN) and peripheral and portal blood samples were recovered and cultured. Several fragments of intestine were taken to determine cell proliferation (PCNA index) and morphometric parameters (villous height, crypt depth). RESULTS: GH, EGF, and INS groups showed a 28%, 29%, and 30% increase in gut mucosal thickness, and PCNA index rose 21%, 20%, and 25%, respectively in comparison with PN controls. Bacterial translocation to peripheral blood was detected in 0% of PN animals and in 44%, 40%, and 28% of GH, EGF, or INS rats, respectively (P < .05). No differences were found in BT in MLN or portal blood among groups. CONCLUSION: Administration of GH, EGF, or INS improves gut mucosal structure in rats with SBS under PN, but, surprisingly, the incidence of BT detected in peripheral blood was increased rather than decreased in animals receiving these treatments.     

Results of growth trophic therapy in children with short bowel syndrome

Purpose

In addition to the structural, ultrastructural, and functional changes that occur after extensive enterectomy or in utero bowel loss that results in short bowel syndrome (SBS), a complex array of humoral responses take place that may also affect adaptation of the remaining small intestine as well as nutritional status or growth. These include alterations in the levels of circulating hormones and trophic substances such as growth hormone (GH) and insulinlike growth factors (IGF-1 and IGFBP-3). The purpose of this investigation is to report on the management/treatment of 3 children with SBS (>4 years in duration) and growth failure.

Methods

Serum measures of growth factors and the response to GH stimulation after an arginine insulin tolerance test (AITT) were determined. Weight and height z-scores as well as linear growth velocity were calculated annually pre- and postinitiation of medication therapy.

Results

Patient 1 (boy, 8.5 years old, midgut volvulus, 18-cm bowel) was found to be GH deficient, whereas patients 2 (girl, 12.5 years old, gastroschisis, 70-cm bowel) and 3 (boy, 9 years old, jejunal atresia, 21 cm bowel) were found to have limited GH responsiveness. Subsequently, treatment with GH (1) and growth releasing factor (GRF; 2 & 3) was prescribed. Z-scores for both weight and height improved over time. Positive linear growth velocity was observed from initiation of therapy (<0.5 cm/yr for all) to more than 3 years of treatment (mean 1, 4.7 cm/yr; 2, 8.7 cm/yr; 3, 5.0 cm/yr [age adjusted normals >4.5, >8.5, and >4.9 cm/yr, respectively]). All patients received a regular diet with oral supplements, whereas 2 received parenteral nutrition support for about 1 year.

Conclusions

In children with medically refractory SBS, it is not only important to offer trophic factors but also essential that sufficient nutrient substrate be provided to achieve adequate growth.     

A useful experimental model of short bowel syndrome.

The short bowel syndrome is a well-known human clinical entity that produces serious metabolic disorders. This syndrome arises after a massive resection of more than 50% of the small intestine, when the intestine attempts to minimize the consequent irregularities by means of compensatory mechanisms. Many reports suggest that an exocrine and endocrine pancreatic dysfunction is associated with enterohormones and an abnormal altered nutrient flow. In this report, we present an experimental model of short bowel syndrome in rats. A massive intestine resection was performed in rats, followed by a histological study of the small intestine. We report the histological changes related to the compensatory changes that occurred in the remaining intestine. The residual intestine produces a hyperplasic response, and hypertrophy was seen in the portion proximal to the anastomosis. We believe this experimental model of short bowel syndrome could be a very useful tool for studying the enterohormonal changes related to an abnormal blood flow of nutrients.     

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.     

Postoperative short bowel syndrome

BACKGROUND: Unanticipated massive resection after intraabdominal procedures is an increasing cause of short bowel syndrome (SBS). Our aim was to determine the frequency and potential mechanisms of postoperative SBS. STUDY DESIGN: We reviewed retrospectively the clinical course of 210 adult patients with SBS evaluated over a 20-year period. RESULTS: Fifty-two (25%) patients had postoperative SBS. The initial operations included colectomy (n=20), hysterectomy (n=8), appendectomy (n=5), gastric bypass (n=5), and other (n=14). Intestinal obstruction (n=38) was the most common reason for resection leading to SBS, either from adhesions (n=26) or volvulus (n=12). Postoperative intestinal ischemia led to resection in 14 patients. SBS occurred from 1 day postoperatively to years later, with 16 (30%) intestinal resections occurring within 1 month. Patients undergoing resection for intestinal ischemia were more likely to undergo resection during the first month than were patients with adhesions and volvulus (86% versus 4% and 25%,respectively, p < 0.05): Patients undergoing resection for ischemia and volvulus were more likely to have remnant length<60 cm compared with those with adhesions (57% and 58% versus 23%, respectively, p < 0.05). Patients undergoing resection for adhesive obstruction were more likely to undergo multiple resections. Thirty-five (67%) patients required longterm parenteral nutrition. Seven (13%) patients died, three in the early postoperative period and four from complications of SBS. CONCLUSIONS: SBS is a potential postoperative complication of intraabdominal procedures and accounts for a considerable proportion of tertiary referrals for SBS. Surgical treatment of postoperative obstruction after common surgical procedures is the most frequent cause. Preventing adhesions, avoiding technical errors, diagnosing a potentially ischemic intestine in a timely manner, and approaching the frozen abdomen cautiously are important strategies for preventing this condition.     

谷氨酰胺和生长激素对短肠综合征患者肠道代偿作用

目的探讨谷氨酰胺和生长激素对短肠综合征(SBS)患者的肠道代偿作用。方法26例短肠综合征患者残余小肠长度为0～100(中位数42.5)cm,手术后接受肠外营养(PN)支持3-52个月,联合应用生长激素(GH)(0.10±0.06)mg·kg-1·d-1和谷氨酰胺(GLN)(0.30±0.17)g·kg-1·d-1进行肠道促代偿治疗。结果26例接受GH加GLN治疗的SBS患者,其中9例(34.6%)治疗后近期内完全摆脱PN;8例(30.8%)经治疗后明显减少了PN用量,从每周需要PN(6.0±1.0)d下降至(4.2±1.0)d,每周PN需要量从(13.6±5.2)L降至(8.2±3.3)L;9例(34.6%)在治疗后仍依赖PN维持。结论经过合适的营养支持和肠道促代偿治疗,大多数短肠综合征患者残留肠道能充分代偿,完全摆脱PN或减少PN用量,长期健康生存。     

精氨酸促进短肠综合征肠道代偿及其机制的初步研究

/L、(13.5±3.0) mg﹒cm-1·100 g-1、(26.0±2.6) μg·cm-1·100 g-1、(59.8±6.2) μg·cm-1·100 g-1、(35.4±2.3) μg·cm-1·100 g-1、(22±3)及(25±3),均P＜0.05];小肠超微结构亦观察到SB-Arg组大鼠小肠绒毛高度、隐窝深度及黏膜厚度均大于SB组大鼠(P＜0.05).结论 肠内营养中添加适量精氨酸能促进短肠综合征大鼠肠道结构及功能的代偿,其机制可能为促进肠黏膜细胞增殖、抑制其凋亡.     

精氨酸促进短肠综合征肠道代偿及其机制的初步研究

目的研究肠内营养中添加精氨酸对广泛肠切除术后大鼠肠道代偿的影响。方法将30只SD大鼠随机分为Con组（假手术）、SB组（短肠对照）和SB—Arg组（短肠加用精氨酸）,各组大鼠于术后第2。14天分别给予等氮、等热量的肠内营养支持．其中SB-Arg组肠内营养中添加L-精氨酸（300mg·kg^-1·d^-1）。比较术后各组体质量、脂肪吸收率、血浆总游离脂肪酸及必需脂肪酸水平、小肠代偿指标、肠黏膜细胞增殖和凋亡的差异。结果SB组术后早期营养支持2周后,其体质量较Con组低,各项肠道代偿指标均明显升高（P〈0．05）。SB-Arg组大鼠脂肪吸收率[（84．9±3．2）％]、血浆游离脂肪酸水平[（650．0±86．5）mg／L]、回肠黏膜质量[（18．0±3．5）mg·cm^-1·100g^-1]、回肠DNA含量[（29．6±3．3）μg·cm^-1·100g^-1]、小肠蛋白质含量[空肠（65．5＋7．3）μg·cm^-1·100g^-1和回肠（39．2±2．3）μg·cm^-1·100g^-1]和小肠增殖指数（空肠31±4,回肠32±2）均高于SB组的[（81．3±3．9）％、（289．5±76．9）mg／L、（13．5±3．0）mg·cm^-1·100g^-1（26．0＋2．6）μg·cm^-1·100g^-1（59．8±6．2）μg·cm^-1·100g^-1、（35．4±2．3）μg·cm^-1·100g^-1、（22±3）及（25±3）,均P〈0．05];小肠超微结构亦观察到SB-Arg组大鼠小肠绒毛高度、隐窝深度及黏膜厚度均大于SB组大鼠（P〈0．05）。结论肠内营养中添加适量精氨酸能促进短肠综合征大鼠肠道结构及功能的代偿．其机制可能为促进肠黏膜细胞增殖、抑制其凋亡。     

Effect of carbon dioxide pneumoretroperitoneum on bacterial translocation in an experimental retroperitoneoscopy model

PURPOSE: To evaluate the effect of artificial CO2 pneumoretroperitoneum on bacterial translocation in an experimental retroperitoneoscopy model. MATERIALS AND METHODS: Eighteen adult male New Zealand White rabbits weighing 2.5 to 3 kg were divided into two groups. Group 1 (control group) consisted of 6 rabbits, while the remaining 12 served as the pneumoretroperitoneum group (group 2). In group 1, the left retroperitoneal space was dissected with a 50-mL balloon without CO2 insufflation, and the animals were kept under anesthesia for 3 hours with the balloons inflated. In group 2, after balloon dissection as in group 1, CO2 insufflation was applied at 1 L/min to achieve a pressure of 10 to 12 mm Hg for 3 hours. Afterward, all animals were sacrificed, and samples were taken from the blood, retroperitoneal area, lungs, liver, mesentery, heart, kidneys, ureters, bladder, colon, small intestine, and spleen and carried to the microbiology laboratory in Carry-Blair medium. Bacterial growth was evaluated using standard techniques. RESULTS: All animals survived the experimental procedures. None of the rabbits in the control group demonstrated any bacterial translocation in the sampled tissues. In the pneumoretroperitoneum group, one rabbit was found to have 10(2) colony-forming units of E. coli in the kidney, but this was considered to be the result of contamination, not translocation. CONCLUSION: Carbon dioxide pneumoretroperitoneum does not seem to cause bacteremia or bacterial translocation in this experimental model. Retroperitoneoscopy probably does not create any additional risk of septic complications.     

Nutritional effects of the serial transverse enteroplasty procedure in experimental short bowel syndrome

Background/Purpose

The serial transverse enteroplasty (STEP) procedure appears beneficial clinically, but the mechanism(s) underlying these effects remains unclear. The present study evaluated the nutritional, hormonal, and morphologic effects of the STEP procedure in a rodent model of short bowel syndrome.

Methods

With institutional animal care ethics approval, Sprague-Dawley rats underwent an 80% distal bowel resection, anastomosing the 30 cm remnant of jejunum to the ascending colon; at day 14, animals were randomly assigned to control or a STEP procedure (n = 8/group). Animals were pair-fed with normal chow; after a further 3 weeks, intestinal transit, hormonal and metabolic balance studies were done, and intestinal tissues were taken for analysis.

Results

The STEP group had increased weight gain (resected: −0.34% ± 2.9% vs STEP: 2.5% ± 1.5%), increased bowel length (34.1 ± 1.5 vs 36.9 ± 2.2 cm), increased jejunal villus height (555 ± 59 vs 635 ± 65 μm), decreased rates of crypt cell apoptosis, increased expression of mRNA for the GLP-2 receptor, and increased postprandial production of glucagon-like peptide 2 (45 ± 14 vs 65 ± 12 pmol/L) (P < .05 by Student t test). There were no differences in intestinal transit; absorption of total calories, protein, fat, or carbohydrate; crypt cell proliferation rates; or the expression of intestinal transporter proteins (SGLT-1, GLUT-2, and GLUT-5).

Conclusions

The STEP procedure improves weight gain and augments gross and microscopic intestinal morphology in severe experimental short bowel syndrome. Postprandial GLP-2 levels are increased, as is the expression of the GLP-2 receptor; these mechanisms may contribute to these metabolic effects and may be useful in guiding the use of the STEP procedure clinically.     

短肠综合征康复治疗的实验与临床研究

目的 研究生长激素对大部小肠切除后残存小肠粘膜增殖活性的影响;评价短肠康复治疗的临床疗效。方法 利用病理图象分析、流式细胞分析、免疫组化法和ＲＴ－ＰＣＲ法观察比较对照组（假手术组）、短肠组（８０％小肠切除）和生长激素组（８０％小肠切除加１Ｕ．ｋｇ＾－１．ｄ＾－１生长激素皮下注射２８ｄ）ＳＤ大鼠小肠粘膜的增殖状况。观察肠康复治疗（肌注生长激素８～１２Ｕ．ｄ＾－１加静脉滴注加谷氨酰胺０．６ｇ．ｋｇ＾－     

Intestinal adaptation in short bowel syndrome

Regaining enteral autonomy after extensive small bowel resection is dependent on intestinal adaptation. This adaptational process is characterized by hyperplastic growth of the remaining gut, which is accompanied by both an increase of cell division at the level of the crypt cells and by an increased rate of programmed cell death (apoptosis). Apart from the absorptive function, the small bowel also has a barrier function and plays an important role in interorgan metabolism. Also, these functions are greatly affected by a massive intestinal resection and subsequent recovery by intestinal adaptation. This review aims to give an overview of the debilitating effects of massive intestinal resection on gut function and subsequently discusses intestinal adaptation and possible factors stimulating adaptation.     

短肠综合征时结肠的代偿研究

目的　观察及评价短肠大鼠结肠代偿性增生及结肠对营养物质吸收的促进作用。　方法　制作切除（80～85）%的超短肠大鼠模型,用百普素(Pepti-2000)做肠内营养（EN）治疗,观察全身营养状况和结肠形态学的改变,并在术后第21天用木糖和15N-甘氨酸混合液对带血管蒂的结肠进行封闭式灌注,观察结肠对水、碳水化合物和氨基酸的吸收情况。　结果　EN组于术后第21天净氮平衡与对照组（CONT）无差异,体重仅比术前减轻(10±18)g。结肠壁明显增厚,皱襞增大增粗,结肠壁的厚度、粘膜厚度、皱襞高度和皱襞表面积与CONT组相比差异具有非常显著性意义（P＜0.01）。EN组与CONT组相比DNA指数1.21±0.11vs.1.01±0.15(P＜0.05),S期细胞百分比（52.6±5.5）%vs.（42.9±4.1）%（P＜0.05）。连续循环灌注3h之后EN组对水、木糖和氨基酸的吸收明显高于CONT组（P＜0.05）。　结论　大鼠结肠在短肠综合征时发生了明显的形态和功能上的代偿。早期适当的肠内营养不但可使超短肠大鼠获得足够营养支持,并且能够促进短肠大鼠结肠代偿。     

短肠综合征的肠内营养支持

目的探讨短肠综合征患者肠内营养支持的临床意义、疗效及注意事项。方法回顾性总结1999至2005年收治的40例短肠综合征患者的临床资料。所有患者均存活至今,并随访2年以上。统计分析其肠内营养用量、费用、脱离肠外营养时间及目前营养状况。结果40例患者平均残存小肠（50．8±29．4）cm,脱离肠外营养平均时间为（29．1±9．2）个月。肠内营养用量为（3284．0±1408．8）kJ／d,其费用显著低于肠外营养（P〈0．01）。目前本组患者平均体质指数为（17．8±3．2）kg,／m^2,血红蛋白（113．3±14．8）g／L,血清白蛋白（35．0±4．1）g／L。平均大便次数为（3．4±1．7）次／d,平均大便量为（720．2±350．3）ml／d。结论肠内营养对于维持短肠综合征患者营养状况、减少并发症具有重要意义,但在具体实施时需掌握方法。     

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.