Model Of Short Bowel Syndrome Research Articles

Saccharomyces boulardii does not stimulate mucosal hyperplasia after intestinal resection in the rat.

Polyamines have been shown to be important regulators of the intestinal adaptation process after massive bowel resection. Saccharomyces boulardii is yeast that has the ability to synthesize polyamines. Therefore. S. boulardii may be useful in the treatment of short bowel syndrome. Twenty 150-g male Sprague-Dawley rats were subjected to 80% jejunoileal resection. Another 20 animals received transection and closure and served as pair fed controls. One half of the resected rats and one half of the controls were given S. boulardii 25 mg/day. After 2 weeks, mucosal mass (mg/cm bowel) did not differ between treated and non-treated animals despite the presence of a marked resection effect. Mucosal DNA, protein, and sucrase activity likewise did not differ. Subsequently, the experiment was repeated four times the original dose (100 mg/day) and found comparable results. In the proximal bowel, mucosal mass was 92+/-6 mg/cm in treated animals versus 107+/-8 mg/cm in untreated rats. In the distal small bowel, comparable values were 85+/-5 mg/cm and 88+/-4 mg/cm. Again, mucosal DNA, protein, and sucrase activity levels paralleled these results. Although S. boulardii may stimulate polyamine synthesis, it does not seem to be helpful in augmenting gut adaptation in this animal model of short bowel syndrome.

Effect of a high fat diet on fatty acid translocase (FAT/CD36) expression and fatty acid transport in isolated enterocytes in a rat model of short bowel syndrome

Sukhotnik, Igor MD; Gork, Semih MD; Coran, Arnold MD; Chen, Min MD; Harmon, Carroll MD, PhD Author Information

Keratinocyte growth factor enhances early gut adaptation in a rat model of short bowel syndrome.

To evaluate the effects of keratinocyte growth factor (KGF) on intestinal adaptation after resection of 85% of the small intestine and consider its potential application in short bowel syndrome (SBS). Experimental study using a known model of SBS. Thirty male Sprague Dawley rats. Four groups of animals were designated. Two groups underwent 85% resection of the small intestine, while the other two groups were sham-operated, undergoing transection and reanastomosis. Resected and sham-operated groups then received either 3 mg/kg KGF or vehicle subcutaneously daily for 3 days. Gut adaptation was evaluated by measurements of mucosal cellularity and biochemical activity in duodenal, jejunal, and ileal segments. Significant small intestinal growth after bowel resection alone was confirmed in resected versus sham-operated rats. KGF further augmented this growth in the resected animals. Mucosal wet weight of the small intestine increased with resection and was further increased (by 20% or more) with KGF administration. Mucosal thickness, villus length, and crypt depth exhibited similar patterns of response. The KGF-induced increase in mucosal morphology was accompanied by increased mucosal DNA and protein content, followed by a trend toward increased mucosal enzyme activity. Histology demonstrated an increase in goblet cells in KGF-treated animals. In situ hybridization analysis demonstrated that KGF markedly increased mucosal expression of intestinal trefoil protein (ITF) mRNA. KGF enhances gut growth, differentiation, and gene regulation during adaptation in rat small intestine after massive resection. KGF may be beneficial in the management of veterinary and human patients undergoing massive intestinal resection.

A successful short-bowel syndrome model in neonatal piglets.

With the higher survival rate of premature neonates as a result of improved neonatal intensive care, the incidence of necrotizing enterocolitis, and thus the incidence of short-bowel syndrome, is increasing. An appropriate animal model resembling the (premature) neonate with short-bowel syndrome suitable for clinically relevant neonatal bowel adaptation and intervention studies, is not available at present. The purpose of this study was the development of a short-bowel syndrome model that mimics the clinical state of the affected neonatal patient. Sixteen 7-day-old piglets received either a small bowel transection (group A) or a 75% resection (group B). The piglets were fed 125 kcal/kg body weight per day, including additional electrolytes. The animals were weighed daily and were killed 28 days after surgery. Bowel samples were obtained at both time points. Mortality rates in groups A and B were 0% and 8%, respectively. Body weight gain was significantly higher in group A than in group B (156% vs. 93%; P = 0.01). Jejunal villus length was higher in group B than in group A (74% vs. -2%; P = 0.006), and crypt depth was higher in group B in both jejunum (201% vs. 67%; P = 0.001) and ileum, (197% vs. 20%; P = 0.001), than in group A. In 7-day-old piglets 75% small bowel resection leads to a clinical short-bowel syndrome, demonstrated by reduced weight gain and typical changes in bowel adaptation parameters. The excellent survival of the animals provides a possibility for the study of bowel adaptation in a neonatal model as well as in intervention studies.

Bacterial translocation in short-bowel syndrome in rats.

Massive intestinal resection results in short-bowel syndrome (SBS) and is associated with an increased risk of infectious complications mainly caused by the egress of intestinal bacteria to distant organs, a process termed bacterial translocation (BT). The purpose of this experimental study in rats was to investigate in different models of SBS the impact of the type of intestinal resection on bacterial growth in the residual small bowel and on the occurrence of BT. SBS was created in 30 rats either by jejunal resection (JR), by ileal resection (IR) or by ileal resection including the ileocecal valve (IR+ICV). 10 animals underwent only a sham laparotomy (SL) and served as controls. Two weeks after the operative procedure, intestinal bacterial colonization and BT to the portal vein, vena cava, mesenteric lymph nodes, liver and spleen were determined. All resected animals showed a decreased weight gain and a significant bacterial overgrowth in the residual small bowel compared to the SL group. BT occurred after SL in 12%, after JR in 70%, after IR in 58%, and was significantly less frequent (35%) after IR+ICV, respectively. These experimental findings suggest that BT in SBS might be promoted by the intestinal bacterial overgrowth in the residual bowel, and the incidence of BT seems to be related to the presence or absence of the ileocecal valve.

SACCAROMYCES BOULARDII DOES NOT STIMULATE MUCOSAL HYPERPLASIA FOLLOWING INTESTINAL RESECTION IN THE RAT

126 Aims:Saccharomyces boulardii is a yeast that has recently been used as a probiotic in the prevention and or treatment of a number of diarrheal disease states. An interesting property of this organism is its ability to synthesize polyamines. The polyamines, spermine, spemidine, and putrascine have been shown to be important regulators of the gut adaptation process, the means whereby gut mass and epithelial surface area increase to accommodate additional nutrient needs following massive bowel resection. We therefore speculated that S. boulardii might be useful in the treatment of short bowel syndrome and chose to investigate the hypothesis that it might be useful in stimulating gut hyperplasia in a well-established rat animal model. This model has been reliable in demonstrating the ability of a number of nutrients and trophic factors to stimulate gut adaptation. Methods: Twenty 150-g male Sprague-Dawley rats were initially subjected to 80% jejunoileal resection, leaving 3 cm of jejunum and 7 cm of ileum intact. Another 20 animals received transsection and closure and served as pair fed controls. One half of the resected rats and one half of controls were given 25 mg/day of S. boulardii per day in their food, all of which was consumed. Animals were pair fed by group, with the animal in each group of four that ate the least, determining the intake of the other three. Animals were sacrificed in two weeks to determine various adaptive parameters. Results: After 2 weeks, mucosal mass (g/cm bowel) did not differ between treated and non-treated animals despite the presence of a marked resection effect. Mucosal DNA and protein likewise did not differ. We subsequently repeated the experiment at 4X the original dose and found comparable results. In the proximal small bowel, mucosal mass (g/cm +/- SEM) was 92 +/- 6 in treated resected animals vs. 107 +/- 8 in untreated rats. In the distal small bowel, comparable values were 85 +/- 5 and 88 +/- 4. Again, mucosal DNA and protein levels paralleled these results. Conclusion: While S. boulardii may stimulate polyamine synthesis, it does not appear to be helpful in augmenting gut adaptation in this animal model of short bowel syndrome.

Keratinocyte growth factor (KGF) enhances early regrowth in a rat model of short bowel syndrome

The effect of KGF on intestinal adaptation was evaluated in an experimental model of short bowel syndrome. Massive intestinal resection was performed in rats in which 85% of the small intestine was removed and the remaining ileal remnant anastomosed to the duodenal stump. Sham operated animals received only an anastomosis after transection. Resected and sham operated animals received 3 mg/kg KGF or vehicle daily for 3 days beginning the day following surgery, weighed daily and pair-fed to standardize the effect of lumenal nutrition. The response was evaluated by measurement of several indices of growth, cellularity and biochemical function in duodenal, jejunal and ileal segments. KGF augmented intestinal growth in the resected as well as the sham operated animal. However, in the case of resection, the weight of residual bowel was increased by 20% in KGF-treated animals. This was in addition to the adaptive hypertrophy that occurs in this resection model. Other indices of growth followed this trend and there were increases in mucosal thickness due to growth of both crypts and villi. The increase in cellularity was also evident by increases in cellular DNA and was accompanied by increased protein, and changes in the alkaline phosphatase and sucrase activities. These data show that KGF can enhance the early regrowth of the small intestine after resection and suggest that KGF may offer benefit to patients undergoing massive small bowel resection by facilitating post-operative intestinal adaptation. This research was funded by Amgen, Inc., Thousand Oaks, CA

Lack of inhibitory effect of octreotide on intestinal adaptation in short bowel syndrome in the rat.

Octreotide is a long-acting analogue of somatostatin, which is effective in the treatment of secretory diarrhea in a number of disorders including short bowel syndrome. Its use in this syndrome has been limited because of concerns about potential adverse effect on intestinal adaptation, because it inhibits a number of trophic hormones. This study was conducted to determine whether octreotide inhibits intestinal adaptation in a rat model of short bowel syndrome. Thirty male Sprague-Dawley rats were divided into four treatment groups, eight receiving 80% small-bowel resection and treated with 2.25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection and treated with 25 microg/kg(-1) per day(-1) of octreotide, eight receiving 80% small-bowel resection with saline control, and six receiving sham operation with saline control. Mucosal weight, protein, and sucrase levels were subsequently analyzed after 2 weeks of therapy. Massive adaptation occurred in all three groups relative to sham-operated controls. However, neither the pharmacologic nor the much higher dose of octreotide demonstrated any adverse effects on intestinal adaptation. In our animal model, octreotide does not inhibit intestinal adaptation after massive small-bowel resection.

Trophic effects of interleukin-11 in rats with experimental short bowel syndrome

Interleukin-11 (IL-11) is a multifunctional cytokine, derived from bone marrow stromal cells, that stimulates proliferation of stem/progenitor precursor cells in the small intestinal crypts and accelerates recovery of intestinal mucosa after cytoablative therapy. This study evaluates whether IL-11 can improve the function and structure of the small intestine and enhance adaptation in an experimental model of short bowel syndrome. After 90% small bowel resection, 32 Sprague-Dawley rats were divided randomly into eight experimental groups of four animals each. Four groups were treated with IL-11 (125 μg/kg twice daily, subcutaneously), and the four control groups were treated with a similar volume (0.1%) of bovine serum albumin (BSA). The animals were weighed daily and were killed on day 2, 4, 6, or 8; remnant small bowel was evaluated for villus height and crypt cell mitosis. The body weight of the animals that received IL-11 was significantly greater at the beginning of postoperative day 4 in comparison to that of the BSA groups (P < .01 during days 5 to 7). The rats that had IL-11 also had significantly greater villus height and crypt cell mitotic rates (P < .05). These observations suggest that IL-11 has a trophic effect on the small bowel during the adaptive phase that follows massive bowel resection and may be useful in the treatment of short bowel syndrome.

Small bowel transplantation for pediatric short bowel syndrome: Evaluation of the graft length required for development and the immunologic aspects relating to graft length

Small bowel transplantation (SBT) is thought to be the only radical treatment for short bowel syndrome in childhood. It is very important that the length of the graft and the type of intestine be chosen carefully because this will determine the outcome of transplantation. This model of short bowel syndrome in the rat confirms that total intestinal resection results in malnutrition and failure to gain weight. After 10 cm of ileum was transplanted orthotopically in a syngeneic combination in rats with total intestinal resection, the animals gained weight. The authors determined that 10 cm of terminal ileum is the minimun length required for survival. Second, the immunologic basis of lethal graft-versus-host reaction (GVHR) as it relates to the intestinal graft length was also evaluated. Ileal grafts of 10 cm from LEW (RT1 1) rats were implanted heterotopically into (LEW × BN)F 1 rats. Ileal grafts of 10 or 40 cm were implanted from BN(RT1 n) rats into (LEW × BN)F 1 animals. A lethal GVHR always occurred after grafting a 10 cm ileum in the LEW F 1 combination, whereas only 17% of the BN F 1 recipients died of typical GVHR. However, in the latter combination, 67% lethal GVHR was induced when 40 cm of the intestinal graft was implanted. These results indicate that mesenteric lymph nodes are a major source of lethal GVHR, but gut-associated lymphoid tissue can also induce this.

Adaptation of jejunal to colonic mucosal autografts in experimentally induced short bowel syndrome

The behavior of jejunal to colonic mucosal autografts was studied in an experimental animal model of short bowel syndrome (SBS). Histological appearances, enterocyte enzyme activities, and in vitro glucose transport were studied at the donor and recipient graft sites in control, short-bowel syndrome, and gastrocolic fistula 5-week-old Sprague-Dawley rats. Small intestinal function was maintained in the jejunocolonic graft after 80% small bowel resection; animals in which small bowel was not resected showed loss of graft function and enzyme activity. This effect is dependent on the presence of jejunal chyme: after gastrocolic fistulae, the jejunum to colon grafts lost jejunal functional activities. Total parenteral nutrition did not alter graft behavior but improved the postoperative mortality of the procedures. The results provide additional information on intestinal adaptation in SBS.

Small-intestinal motility in a newborn model of short-bowel syndrome

Small-intestinal motility in a newborn model of short-bowel syndrome

Essential fatty acid deficiency and postresection mucosal adaptation in the rat

The effect of short-term (biochemical) and long-term (clinical) essential fatty acid (EFA) deficiency on mucosal adaptation was studied in a surgical model of short bowel syndrome. Rats fed an EFA-deficient diet for 4 wk had biochemical evidence of EFA deficiency (hepatic and red blood cell triene to tetraene ratios > 0.4). Resected animals (70% proximal jejunoileal resection) receiving an EFA-deficient diet had a significantly impaired intestinal mucosal hyperplasia response in all remaining small bowel segments compared with resected controls. The effect of refeeding a control diet to clinically EFA-deficient resected rats was also evaluated. Short-term refeeding (2 wk) of a control diet resulted in a significant return toward normal tissue triene to tetraene ratios. Concomitantly, refed animals had significantly greater mucosal adaptation in the remaining duodenal/jejunal segment compared with resected animals maintained on an EFA-deficient diet postoperatively. These experiments underscore the dynamic nature of tissue EFA status and the importance of fatty acids in the normal compensatory mechanisms of mucosal adaptation after resection.