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Objectives: Parenteral nutrition is a critically important intervention for children with intestinal dysfunctions. However, total parenteral nutrition (TPN) with no enteral feeding is associated with small intestine atrophy and malabsorption, which complicate the transition to enteral nutrition. The objective of the present study was to evaluate the therapeutic potential of the intestinotrophic peptide glucagon-like peptide 2 (GLP-2), which reduces TPN-associated atrophy and maintains nutrient absorption in adult rats, for preventing nutrient malabsorption in neonates receiving TPN., Methods: Term pigs obtained by cesarean delivery received from birth TPN alone (TPN; n = 7) or TPN with GLP-2 (25 nmol . kg(-1) . d(-1); GLP-2; n = 8) or were fed sow milk enterally (n = 7). The small intestine was removed on postnatal day 6 to measure morphological responses and absorption of glucose, leucine, lysine and proline by intact tissues and brush border membrane vesicles and to quantify the abundances of mRNA and protein for enterocyte glucose transporters (SGLT-1 and GLUT2)., Results: Relative to TPN alone, administration of GLP-2 resulted in small intestines that were larger (P < 0.01), had greater abundances of mRNA and protein for SGLT-1, but not for GLUT2, and had higher capacities to absorb nutrients (P < 0.01). Moreover, the intestines of GLP-2 pigs were comparable in size and absorptive capacities with those of pigs fed sow milk enterally., Conclusions: Providing GLP-2 to neonates receiving TPN prevents small intestine atrophy, results in small intestine absorptive capacities that are comparable to when nutrients are provided enterally and may accelerate the transition from TPN to enteral nutrition.

Background: Early enteral nutrition in patients following traumatic injury is an important intervention. However, after shock-resuscitation, intestinal hypoperfusion persists despite adequate systemic resuscitation. Our previous in vivo rat studies indicate that hypoperfusion impairs mucosal function in the small intestine. Therefore, the current study sought to improve previous in vitro models by the following means: (1) We used Caco-2 monolayers stably transfected with the brush-border sodium-glucose co-transporter (SGLT-1); and (2) we created an environment that mimicked the physiologic enterocyte environment. We hypothesized that hypoxic alterations of epithelial function in an in vitro model are comparable to those of an in vivo rat model., Methods: After 21 days, monolayers were randomized to receive 24 hours of incubation in a normoxic or hypoxic environment. Cells were further randomized to receive 1 of 4 nutrient treatments: mannitol (an osmotic control), glucose (uses SGLT-1 and is metabolized), 3-O-methylglucose (3-O-mg; uses SGLT-1 and is not metabolized), or fructose (does not use SGLT-1 but can be metabolized)., Results: Transepithelial resistance (p = .007) and short-circuit current (p = .05) were lower in hypoxic groups. When compared with normoxic groups, hypoxic groups had significantly impaired glucose (p < .001) but not glutamine transport, irrespective of nutrient treatment. Additionally, adenosine triphosphate/adenosine diphosphate ratio was reduced (p = .01) and lactate concentration was increased (p < .001) during hypoxia., Conclusions: In summary, results from this in vitro study using Caco-2BBe cells stably transfected with SGLT-1 correspond to results obtained in the in vivo rat model. Therefore, this is an appropriate in vitro model in which to study cellular alterations caused by the hypoxic small intestine, with the goal of ensuring safe early enteral nutrition following traumatic injury.

Background: Provision of enteral nutrients shortly after traumatic injury has become the preferred method of nutrition support provided to patients. However, traumatic shock results in splanchnic hypoperfusion, which may cause persistent intestinal hypoxia. This study tested the hypothesis that delivery of enteral nutrients to the hypoperfused jejunum increases oxidative demand beyond that available, thereby exacerbating intestinal hypoxia., Methods: Wistar-Furth rats (186+/-4 g; n = 24) were randomized to receive intestinal hypoxia (superior mesenteric artery occlusion) or serve as normoxic controls (sham laparotomy). Within the jejunum of each rat, 4 6-cm loops were randomized to receive luminal perfusions with 1 of 4 substrates: mannitol (an osmotic control); glucose (undergoes active transport via the sodium-glucose co-transporter [SGLT-1] and is metabolized); 3-o-methylglucose (3-o-mg; uses SGLT-1 but is not metabolized); or fructose (does not use SGLT-1 but is metabolized). After in situ perfusions, jejunal tissue was removed for analysis of nutrient transport and barrier function in modified Ussing chambers. Tissue homogenate was used to determine concentration of ATP, lactate, pyruvate, and protein. Also, jejunal tissue was stained with hematoxylin and eosin for qualitative analysis of ischemia and necrosis., Results: Transmural resistance was lower (p < .001) in the hypoxia groups, irrespective of substrate, indicating increased mucosal permeability. When compared with the normoxic controls, glucose transport was impaired (p < .001) in the hypoxic groups; however, glutamine transport was unaffected. The degree of intestinal hypoxia, assessed by jejunal lactate concentration, was higher (p < .001) in the glucose and fructose groups, than the control mannitol and 3-o-mg groups., Conclusions: The observation that 3-o-mg did not differ from the mannitol control indicates that SGLT-1 activation alone does not exacerbate hypoxia. Rather, these results indicate that provision of metabolizable nutrients to the hypoperfused intestine exacerbate hypoxia and potentially lead to intestinal ischemia. Although early enteral nutrition is an important intervention after trauma, care must be taken to ensure intestinal perfusion is adequate to allow for nutrient metabolism and prevent further compromise.

Background: Intestinal adaptation is a complex physiological process that is not completely understood. Systemic administration of short-chain fatty acids (SCFAs) has been shown to facilitate adaptation to small bowel resection; however the mechanisms underlying this phenomena are unknown., Methods: Forty-six male Sprague-Dawley rats underwent an 80% jejunoileal resection and jugular catheterization. After surgery, rats were randomly assigned to receive standard total parenteral nutrition (TPN) or an isoenergetic, isonitrogenous TPN supplemented with SCFAs. On day 3 or 7 after surgery, ileal samples were removed for determination of mucosal wet weight, DNA, RNA, and protein concentrations. Total cellular RNA was extracted for use in Northern blot analysis to quantify proglucagon and ornithine decarboxylase messenger RNAs (mRNAs)., Results: Total, mucosal, and submucosal weights were increased (p < .05) in the SCFA group both 3 and 7 days after surgery. Ileal DNA and RNA concentrations were increased (p < .05) in the SCFA group at both time points; however ileal protein concentration did not differ between groups until 7 days after resection. Levels of proglucagon and ornithine decarboxylase messenger RNAs were higher (p < .05) in the SCFA group at both time points., Conclusion: The upregulation of proglucagon and ornithine decarboxylase gene expression may be the mechanism by which SCFAs facilitate intestinal adaptation.

Background: Total parenteral nutrition (TPN) alters both specific and nonspecific immune functions, resulting in immunosuppression. Short-chain fatty acids have been shown to improve the adaptive responses of the gut after surgery. The following study investigates the effects of adding short-chain fatty acids to TPN on the immune system after an 80% small bowel resection., Methods: Rats (237 +/- 3 g) were infused with either TPN (n = 25) or TPN supplemented with short-chain fatty acids (n = 26) for 3 or 7 days. Hematologic analysis was performed on peripheral blood and splenocytes were isolated to characterize cell phenotypes, natural killer cell cytotoxicity and to estimate proliferative response., Results: The relative percent of T (CD3+) cells increased (p < .05) and the relative percent of macrophages decreased (p < .001, n = 13) in the spleens of the 3-day TPN-fed rats. By day 7, these differences disappeared. The natural killer cells from rats that were supplemented with short-chain fatty acids had higher (p < .0001) cytotoxic activity than the TPN groups at day 3. Mitogenic response did not differ between groups but were depressed compared with sham-treated rats. By day 7, rats on standard TPN had larger (p < .0001) spleens than all other groups. This group also had a higher total white blood cell count because of increased numbers of macrophages and neutrophils (p < .02)., Conclusion: Short-chain fatty acids improve components of nonspecific immune responses and may be beneficial in reducing certain aspects of TPN-associated immunosuppression after major surgery.