Mechanisms of Enteral Nutrient-Enhanced Intestinal Adaptation
2006; Elsevier BV; Volume: 130; Issue: 2 Linguagem: Inglês
10.1053/j.gastro.2005.11.051
ISSN1528-0012
Autores Tópico(s)Digestive system and related health
ResumoThe role of enteral nutrients in maintaining small intestinal structure and function is well established. Evidence that enteral nutrients induce intestinal adaptation include the structural and functional gradient along the length of the healthy intestine, the atrophy and functional compromise induced by fasting and parenteral nutrition, and the enhanced adaptive capacity of the distal intestine following partial enterectomy. Key mechanisms contributing to enteral nutrient-induced intestinal adaptation include nonspecific luminal stimulation and that provided by specific nutrients, “functional workload” induced by polymeric nutrients, potential stimulation of pancreaticobiliary secretions, secretion of humoral mediators, and induction of intestinal hyperemia. The role of enteral nutrients in maintaining small intestinal structure and function is well established. Evidence that enteral nutrients induce intestinal adaptation include the structural and functional gradient along the length of the healthy intestine, the atrophy and functional compromise induced by fasting and parenteral nutrition, and the enhanced adaptive capacity of the distal intestine following partial enterectomy. Key mechanisms contributing to enteral nutrient-induced intestinal adaptation include nonspecific luminal stimulation and that provided by specific nutrients, “functional workload” induced by polymeric nutrients, potential stimulation of pancreaticobiliary secretions, secretion of humoral mediators, and induction of intestinal hyperemia. Intestinal adaptation has been the focus of stimulating research efforts for more than a century since Senn1Senn N. An experimental contribution to intestinal surgery with special reference to the treatment of intestional obstruction. II Enterectomy.Ann Surg. 1888; 7: 99-115Crossref PubMed Google Scholar and later Flint2Flint J. The effect of extensive resection of the small intestine.Bull Johns Hopkins Hosp. 1912; 23: 127-144Google Scholar sparked interest with their initial observations of this phenomenon. Intestinal adaptation refers to a process wherein the intestine undergoes various structural and functional alterations to compensate for loss of intestinal function because of injury or resection. Given the contemporary definition of intestinal failure as “reduced intestinal absorption so that macronutrient and/or water and electrolyte supplements are needed to maintain health or growth,”3Nightingale J.M. The medical management of intestinal failure methods to reduce the severity.Proc Nutr Soc. 2003; 62: 703-710Crossref PubMed Scopus (60) Google Scholar optimization of intestinal adaptation is of fundamental importance to the medical management of patients with intestinal failure.The important role of enteral nutrients in intestinal adaptation is well established. The purpose of this review is to discuss evidence that enteral nutrients induce both structural and functional indices of intestinal adaptation. In addition, factors hypothesized to be part of the multifactorial mechanism whereby enteral nutrients stimulate intestinal adaptation will be explored.Evidence That Enteral Nutrients Induce Intestinal AdaptationStructural Gradient of Healthy Intestinal MucosaMuch of the evidence supporting the concept that enteral nutrients are trophic to the small intestinal mucosa has been appealing in that it is gradient based. Histologic examination of human jejunum and ileum displays a clear structural gradient4Madara J.L. Trier J.S. The functional morphology of the mucosa of the small intestine.in: Johnson L.R. Physiology of the gastrointestinal tract. 3rd ed. Raven Press, New York1994: 1577-1622Google Scholar that is consistent with the proximal to distal continuum of nutrient concentrations within the small intestine. Transmural width of the intestine is greater in the jejunum than the ileum, with a gradual diminution in the caliber of the lumen from the duodenum to ileum. The plica circularis are thick, tall, and numerous in the proximal jejunum and become less frequent in the ileum. The villi of the proximal small intestine are as long as 0.8 mm with a leaf or finger shape, whereas the villi of the ileum rarely exceed 0.5 mm in length and are limited to the finger shape.Beyond the amplified surface area of the proximal small intestine, the digestive and absorptive capacity of this region is further augmented by increased expression of key nutrient processing proteins within each enterocyte. Intact villi from mouse jejunum were found to be 8-fold more effective than ileal villi in disaccharide hydrolysis, despite only a 3-fold increase in villus surface area.5James P.S. Smith M.W. Tivey D.R. Single-villus analysis of disaccharidase expression by different regions of the mouse intestine.J Physiol. 1988; 401: 533-545Crossref PubMed Scopus (17) Google Scholar The direct effect of enteral nutrients may also explain this proximal-to-distal gradient in intestinal function because of substrate-induced regulation of key nutrient processing proteins. It is well established that the activity of most macronutrient transporters studied, including those transporting monosaccharides, amino acids, and peptides, are regulated by the dietary levels of their substrates.6Ferraris R.P. Diamond J.M. Specific regulation of intestinal nutrient transporters by their dietary substrates.Annu Rev Physiol. 1989; 51: 125-141Crossref PubMed Scopus (236) Google ScholarFasting Impairs Intestinal Structure and FunctionThe stimulatory role provided by enteral nutrients is further supported by evidence indicating that fasting alters small intestinal structure and function. The intestine is particularly susceptible to the metabolic insult provided by fasting as the enteric mucosal and muscular layers atrophy to a disproportionate degree compared with the changes in total body mass and weight of other tissues.7Steiner M. Bourges H.R. Freedman L.S. Gray S.J. Effect of starvation on the tissue composition of the small intestine in the rat.Am J Physiol. 1968; 215: 75-77PubMed Google Scholar, 8McManus J.P. Isselbacher K.J. Effect of fasting versus feeding on the rat small intestine. Morphological, biochemical, and functional differences.Gastroenterology. 1970; 59: 214-221Abstract Full Text PDF PubMed Google Scholar In the laboratory rat, a 72-hour fast results in a reduction in mucosal mass that is approximately 3-fold greater than the associated reduction in body weight.9Kotler D.P. Levine G.M. Shiau Y.F. Effects of luminal nutrition and metabolic status on in vivo glucose absorption.Am J Physiol. 1981; 240: G432-G436PubMed Google Scholar Fasting-induced reductions in mucosal surface area also impacted intestinal function because glucose absorption was approximately 2-fold higher (per centimeter intestinal length) in animals consuming enteral nutrients. Epithelial ion transport is also perturbed during fasting6Ferraris R.P. Diamond J.M. Specific regulation of intestinal nutrient transporters by their dietary substrates.Annu Rev Physiol. 1989; 51: 125-141Crossref PubMed Scopus (236) Google Scholar and can occur prior to changes in intestinal surface area.10Carey H.V. Effects of fasting and hibernation on ion secretion in ground squirrel intestine.Am J Physiol. 1992; 263: R1203-R1208PubMed Google Scholar Fluid and electrolyte losses are increased during fasting because of increased epithelial secretion under basal and stimulated conditions (for a thorough review, see Ferraris and Carey11Ferraris R.P. Carey H.V. Intestinal transport during fasting and malnutrition.Annu Rev Nutr. 2000; 20: 195-219Crossref PubMed Scopus (152) Google Scholar). Fasting also impairs intestinal barrier function by increasing epithelial permeability to ions and macromolecules and exposing the host to the risk of luminal antigens. These data underscore the concept that intestinal function and structure are independently regulated from both a time and trigger perspective. However, the response of the intestinal mucosa to the absence of enteral nutrients as assessed during fasting is clearly confounded by the effects of malnutrition. Therefore, the effect of total parenteral nutrition on the small intestinal mucosa presents an ideal model to study the role of enteral nutrients while providing adequate nutritional requirements.Administration of Nutrients Parenterally Induces Intestinal AtrophyThe structural impairments that occur in the gastrointestinal tract during fasting also occur when nutrient requirements are provided through total parenteral nutrition. The 60% reduction in mucosal weight that occurred following a 72-hour fast also took place in animals receiving the nutrient requirements parenterally, despite maintenance of body weight.9Kotler D.P. Levine G.M. Shiau Y.F. Effects of luminal nutrition and metabolic status on in vivo glucose absorption.Am J Physiol. 1981; 240: G432-G436PubMed Google Scholar Johnson et al12Johnson L.R. Copeland E.M. Dudrick S.J. Lichtenberger L.M. Castro G.A. Structural and hormonal alterations in the gastrointestinal tract of parenterally fed rats.Gastroenterology. 1975; 68: 1177-1183Abstract Full Text PDF PubMed Scopus (70) Google Scholar demonstrated that rats maintained exclusively on parenteral nutrients for up to 3 weeks exhibited a 73% reduction in small intestinal weight compared with enterally fed controls. The small intestine of the parenterally fed animals exhibited a 50% loss of DNA, indicating a significant decrease in cellularity. Evidence of mucosal atrophy associated with parenteral nutrients in humans is less striking but present nonetheless. In healthy volunteers, 3 weeks of total parenteral nutrition decreased total mucosal thickness by 20% compared with that obtained at baseline.13Buchman A.L. Moukarzel A.A. Bhuta S. Belle M. Ament M.E. Eckhert C.D. Hollander D. Gornbein J. Kopple J.D. Vijayaroghavan S.R. Parenteral nutrition is associated with intestinal morphologic and functional changes in humans.JPEN J Parenter Enteral Nutr. 1995; 19: 453-460Crossref PubMed Scopus (348) Google Scholar This intestinal atrophy was associated with a near doubling in intestinal permeability, as assessed by the urinary lactulose-mannitol ratio, and a 10% decrease in epithelial cell number that was reversible on 5 days of enteral refeeding. When compared with orally fed children, those receiving long-term (>9 months) parenteral feeding exhibited mild villus atrophy and a 63% lower incorporation of 3H-thymidine per milligram of intestine, indicating a reduced level of cellular proliferation.14Rossi T.M. Lee P.C. Young C. Tjota A. Small intestinal mucosa changes, including epithelial cell proliferative activity, of children receiving total parenteral nutrition (TPN).Dig Dis Sci. 1993; 38: 1608-1613Crossref PubMed Scopus (62) Google Scholar These studies suggest that the intestinal response to the parenteral, versus luminal, provision of nutrients in humans is in general agreement with the hypoplastic effect observed in animals.Total parenteral nutrition also inhibits several functional attributes of the small intestine. The activity of several brush-border hydrolases decreases (sucrase [79%], maltase [72%], lactase [81%], glucoamylase [83%], acid aminopeptidase [78%], dipeptidyl peptidase [40%]) following 21 days of total parenteral nutrition in mucosa of the human duodenum.15Guedon C. Schmitz J. Lerebours E. Metayer J. Audran E. Hemet J. Colin R. Decreased brush border hydrolase activities without gross morphologic changes in human intestinal mucosa after prolonged total parenteral nutrition of adults.Gastroenterology. 1986; 90: 373-378PubMed Google Scholar This functional consequence to the absence of enteral nutrients is rapidly reversible upon oral refeeding and distinctly outpaces structural alterations as only modest reductions (13%) in microvillus height occurred in this trial. Total parenteral nutrition also impacts brush-border nutrient transport in the human small intestine. Following 7 days of total parenteral nutrition, brush-border membrane vesicles prepared from the small intestinal mucosa of surgical patients exhibited 26%–44% decreases in carrier-mediated transport velocity of many substrates including D-glucose, L-alanine, L-arginine, and L-leucine but not L-glutamine.16Inoue Y. Espat N.J. Frohnapple D.J. Epstein H. Copeland E.M. Souba W.W. Effect of total parenteral nutrition on amino acid and glucose transport by the human small intestine.Ann Surg. 1993; 217: 604-614Crossref PubMed Scopus (52) Google Scholar Interestingly, ample data obtained in animal models indicate that, when luminal nutrients are lacking, as with total parenteral nutrition, there is actually an increase in the specific activity of many nutrient transporters within the mucosal protein pool.9Kotler D.P. Levine G.M. Shiau Y.F. Effects of luminal nutrition and metabolic status on in vivo glucose absorption.Am J Physiol. 1981; 240: G432-G436PubMed Google Scholar, 17Howard A. Goodlad R.A. Walters J.R. Ford D. Hirst B.H. Increased expression of specific intestinal amino acid and peptide transporter mRNA in rats fed by TPN is reversed by GLP-2.J Nutr. 2004; 134: 2957-2964Crossref PubMed Scopus (48) Google Scholar However, these effects are greatly overwhelmed by loss of epithelial mass resulting in reduced functional capacity. Although the available evidence indicate that enteral nutrients are needed to maintain the digestive and absorption capacity of the human intestinal mucosa, additional studies are needed to determine the relationship between structural and functional consequences and the minimal amount of enteral nutrient consumption required to prevent mucosal alterations.Adaptive Capacity of Ileum Exceeds That of JejunumGiven the evidence that reducing exposure to luminal nutrients negatively impacts the intestinal mucosa, can increasing exposure to enteral nutrients result in an expanded epithelial surface area with enhanced functional capacity? To answer this question, the pioneering work of Dowling and Booth18Dowling R.H. Booth C.C. Structural and functional changes following small intestinal resection in the rat.Clin Sci. 1967; 32: 139-149PubMed Google Scholar subjected rats to a 70% resection of either the proximal or distal small intestine. Compared with transected control animals, villus height in the remnant jejunum increased 14%, whereas that of the remnant ileum increased 53%. Using an in situ perfusion model, glucose absorption in the remnant jejunum increased 18%, whereas the increase observed in the remnant ileum was 96%. These data clearly demonstrate that the ileal mucosa responds both structurally and functionally when the concentration of nutrients presented to the brush-border membrane is increased. However, the modest but statistically significant changes in the remnant jejunum support the argument that these data do not solely examine the effect of enteral nutrient exposure on the intestinal mucosa but are confounded by the trophic stimuli provided by intestinal resection and the starting differences inherent in crypt-villous architecture between the jejunum and ileum. Therefore, Dowling and Booth18Dowling R.H. Booth C.C. Structural and functional changes following small intestinal resection in the rat.Clin Sci. 1967; 32: 139-149PubMed Google Scholar also performed ileo-jejunal transposition studies in rats to eliminate the stimuli provided by intestinal resection and isolate the effect of enteral nutrient concentration. Compared with sham controls, transposition of the jejunum to the distal portion of the small intestine did not alter glucose transport. However, in the juxtaposed ileum, marked villus hypertrophy occurred and was associated with a 2.5-fold increase in glucose absorption.In summary, ample evidence exists indicating that the enteral nutrients enhance structural and functional attributes of the small intestine. In fact, the marked structural and functional adaptations that occur in the ileum following intestinal resection are abolished when nutrients are provided parenterally, rather than enterally.19Feldman E.J. Dowling R.H. McNaughton J. Peters T.J. Effects of oral versus intravenous nutrition on intestinal adaptation after small bowel resection in the dog.Gastroenterology. 1976; 70: 712-719Abstract Full Text PDF PubMed Scopus (295) Google Scholar However, one must be cautious in suggesting that the topical exposure to nutrients is exclusively trophic to the small intestinal mucosa without considering the impact of specific nutrients, endogenous secretions, gastrointestinal hormones, and hyperemia provoked by the consumption of oral nutrients.What Are the Potential Mechanisms Associated With These Effects?Generalized Effects of Luminal NutrientsWhen contemplating the generalized mechanisms whereby luminal nutrients may stimulate structural and functional adaptations in the intestinal mucosa, it is important to note that the heightened adaptive capacity of the residual ileum following a proximal resection is dependent on enteral stimulation. This reliance of the adapting mucosa on enteral nutrients may be related to a sensitive feedback system involving malabsorbed nutrients reaching the distal gastrointestinal tract, the commensal microbiota, and the resulting production of short-chain fatty acids (SCFA).The impact of SCFAs on the intestinal mucosa will be discussed extensively by Drs Kles and Chang in this supplement; however, SCFA’s impact on the intestinal mucosa is worthy of a brief mention here when considering the generalized effects of luminal nutrients on intestinal adaptation. There is a growing body of research supporting a trophic role for SCFA in the small intestine. Intestinal adaptation to resection is increased with the ingestion of fermentable dietary fiber.20Koruda M.J. Rolandelli R.H. Settle R.G. Saul S.H. Rombeau J.L. The effect of a pectin-supplemented elemental diet on intestinal adaptation to massive small bowel resection.JPEN J Parenter Enteral Nutr. 1986; 10 (Harry M. Vars award): 343-350Crossref PubMed Scopus (108) Google Scholar, 21Kripke S.A. Fox A.D. Depaula J.A. Berman J.M. McGinty R. Settle R.G. Rombeau J.L. Pectin supplemented elemental diet improves outcome in short bowel syndrome.Am J Clin Nutr. 1988; 47: 759Google Scholar, 22Tsukahara T. Iwasaki Y. Nakayama K. Ushida K. Stimulation of butyrate production in the large intestine of weaning piglets by dietary fructooligosaccharides and its influence on the histological variables of the large intestinal mucosa.J Nutr Sci Vitaminol. 2003; 49 (Tokyo): 414-421Crossref PubMed Scopus (87) Google Scholar Reduction of cecal SCFA content with antibiotic treatment decreases postresection adaptation,23Aghdassi E. Plapler H. Kurian R. Raina N. Royall D. Jeejeebhoy K.N. Cohen Z. Allard J.P. Colonic fermentation and nutritional recovery in rats with massive small bowel resection.Gastroenterology. 1994; 107: 637-642Abstract Full Text PDF PubMed Scopus (20) Google Scholar whereas intracolonic infusion of SCFA in germ-free animals stimulates mucosal growth. As a topic of recent controversy, Juno et al24Juno R.J. Knott A.W. Jarboe M.D. Profitt S.A. Erwin C.R. Warner B.W. Characterization of small bowel resection and intestinal adaptation in germ-free rats.Surgery. 2003; 134: 582-590Abstract Full Text Full Text PDF PubMed Scopus (11) Google Scholar reported that the commensal microbiota are not involved in, and may actually attenuate, the proliferative response of the mucosal epithelium following intestinal resection; however, these authors state that this effect may relate to the duration of the antibiotic administration within these trials.Parenteral nutrition supplemented with SCFA significantly reduces the ileal mucosa atrophy associated with unsupplemented parenteral nutrition25Koruda M.J. Rolandelli R.H. Bliss D.Z. Hastings J. Rombeau J.L. Settle R.G. Parenteral nutrition supplemented with short-chain fatty acids effect on the small-bowel mucosa in normal rats.Am J Clin Nutr. 1990; 51: 685-689PubMed Google Scholar and enhances adaptive markers following small bowel resection.26Koruda M.J. Rolandelli R.H. Settle R.G. Zimmaro D.M. Rombeau J.L. Effect of parenteral nutrition supplemented with short-chain fatty acids on adaptation to massive small bowel resection.Gastroenterology. 1988; 95: 715-720Abstract Full Text PDF PubMed Scopus (132) Google Scholar Work from our laboratory has determined that the supplementation of parenteral nutrition with SCFA enhanced structural and functional adaptation in both adult rats27Tappenden K.A. Thomson A.B. Wild G.E. McBurney M.I. Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.JPEN J Parenter Enteral Nutr. 1996; 20: 357-362Crossref PubMed Scopus (90) Google Scholar, 28Tappenden K.A. Thomson A.B. Wild G.E. McBurney M.I. Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats.Gastroenterology. 1997; 112: 792-802Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar and neonatal piglets29Albin D.M. Bartholome A.L. Tappenden K.A. Glucose transport is enhanced by short-chain fatty acid supplemented-total parenteral nutrition in a piglet model of intestinal adaptation.9th International Symposium on Digestive Physiology of Pigs. 2003Google Scholar, 30Albin D.M. Bartholome A.L. Tappenden K.A. Amino acid and dipeptide transport are enhanced by short-chain fatty acid supplemented-total parenteral nutrition in a piglet model of intestinal adaptation.9th International Symposium on Digestive Physiology of Pigs. 2003Google Scholar, 31Bartholome A.L. Albin D.M. Baker D.H. Holst J.J. Tappenden K.A. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.JPEN J Parenter Enteral Nutr. 2004; 28: 210-223Crossref PubMed Scopus (137) Google Scholar following massive small bowel resection. It appears that butyrate is the SCFA responsible for augmenting structural aspects of intestinal adaptations by increasing proliferation and decreasing apoptosis as early as 4 hours postresection.31Bartholome A.L. Albin D.M. Baker D.H. Holst J.J. Tappenden K.A. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.JPEN J Parenter Enteral Nutr. 2004; 28: 210-223Crossref PubMed Scopus (137) Google Scholar Furthermore, it is not clear whether butyrate mediates these responses directly or via a potential mechanism(s) relating to induced expression of the intestinotrophic peptide glucagon-like peptide-2 (GLP-2).27Tappenden K.A. Thomson A.B. Wild G.E. McBurney M.I. Short-chain fatty acids increase proglucagon and ornithine decarboxylase messenger RNAs after intestinal resection in rats.JPEN J Parenter Enteral Nutr. 1996; 20: 357-362Crossref PubMed Scopus (90) Google Scholar, 28Tappenden K.A. Thomson A.B. Wild G.E. McBurney M.I. Short-chain fatty acid-supplemented total parenteral nutrition enhances functional adaptation to intestinal resection in rats.Gastroenterology. 1997; 112: 792-802Abstract Full Text Full Text PDF PubMed Scopus (114) Google Scholar, 31Bartholome A.L. Albin D.M. Baker D.H. Holst J.J. Tappenden K.A. Supplementation of total parenteral nutrition with butyrate acutely increases structural aspects of intestinal adaptation after an 80% jejunoileal resection in neonatal piglets.JPEN J Parenter Enteral Nutr. 2004; 28: 210-223Crossref PubMed Scopus (137) Google Scholar The presence of malabsorbed enteral nutrients stimulating intestinal adaptation in the distal intestine is supported by a report from Ziegler et al.32Ziegler T.R. Fernandez-Estivariz C. Gu L.H. Bazargan N. Umeakunne K. Wallace T.M. Diaz E.E. Rosado K.E. Pascal R.R. Galloway J.R. Wilcox J.N. Leader L.M. Distribution of the H+/peptide transporter PepT1 in human intestine up-regulated expression in the colonic mucosa of patients with short-bowel syndrome.Am J Clin Nutr. 2002; 75: 922-930Crossref PubMed Scopus (157) Google Scholar In colonic biopsy specimens from subjects with short bowel syndrome, compared with control subjects with normal intact intestines, the messenger RNA (mRNA) abundance of PepT1, the di- and tripeptide transporter in the intestine, was increased 5-fold. The mechanism responsible for this increase has not been described at this point but could involve substrate-induced regulation of nutrient transporters based on the appearance of these nutrients within distal portions of the gastrointestinal tract. Alternatively, these malabsorbed enteral nutrients may reach the distal intestine and augment SCFA production via fermentation by the commensal microbiota. Although confirmation of these hypotheses awaits further testing, etiologically, such a scenario would provide ideal mechanisms whereby malabsorbed nutrients could stimulate structural and functional aspects of intestinal adaptation and thereby enhance the digestive and absorptive processing capacity of the intestine.Nutrient Composition and ComplexityThe specific dietary components of the enteral nutrition supplied have been shown to alter the structural and functional characteristics of the adaptive response. Following massive small bowel resection, the provision of enteral lipid,33Sukhotnik I. Mor-Vaknin N. Drongowski R.A. Coran A.G. Harmon C.M. Effect of dietary fat on fat absorption and concomitant plasma and tissue fat composition in a rat model of short bowel syndrome.Pediatr Surg Int. 2004; 20: 185-191Crossref PubMed Scopus (21) Google Scholar but not parenteral lipid,34Dahly E.M. Grahn M.J. Draxler A.K. Ney D.M. Intestinal adaptation occurs independently of parenteral long-chain triacylglycerol and with no change in intestinal eicosanoids after mid-small bowel resection in rats.J Nutr. 2004; 134: 112-119PubMed Google Scholar augmented and accelerated the adaptive process. Free fatty acids appear to be more potent than long-chain triglycerides, protein, starch, or medium-chain triglycerides in enhancing many morphologic aspects of intestinal adaptation.35Morin C.L.G.V. Garofalo C. Influence of lipids on intestinal adaptation after resection.in: Robinson J.W.L. Dowling T.H. Riecken E.-O. Mechanisms of intestinal adaptation. MTP Press Ltd, 1982Google Scholar, 36Grey V.L. Garofalo C. Greenberg G.R. Morin C.L. The adaptation of the small intestine after resection in response to free fatty acids.Am J Clin Nutr. 1984; 40: 1235-1242PubMed Google Scholar However, among long-chain fatty acids, eicosapentanoic and docosahexanoic acids are more effective in inducing structural changes associated with adaptation than less highly unsaturated fats.37Vanderhoof J.A. Park J.H. Herrington M.K. Adrian T.E. Effects of dietary menhaden oil on mucosal adaptation after small bowel resection in rats.Gastroenterology. 1994; 106: 94-99Abstract PubMed Google ScholarHigh-protein diets have been noted to stimulate amino acid transport across the jejunum in vivo38Scharrer E. Adaptation of intestinal amino acid transport.Experientia. 1972; 28: 159-267Crossref Scopus (17) Google Scholar as well as in vitro.39Lis M.T. Crampton R.F. Matthews D.M. Effect of dietary changes on intestinal absorption of L-methionine and L-methionyl-L-methionine in the rat.Br J Nutr. 1972; 27: 159-167Crossref PubMed Scopus (70) Google Scholar Using a juvenile pig model of short bowel syndrome, supplementation of a polymeric formula with colostrum protein concentrate enhanced villus length and crypt depth throughout the remnant intestine with a resulting increase in overall growth compared with control animals.40Nagy E.S. Paris M.C. Taylor R.G. Fuller P.J. Sourial M. Justice F. Bines J.E. Colostrum protein concentrate enhances intestinal adaptation after massive small bowel resection in juvenile pigs.J Pediatr Gastroenterol Nutr. 2004; 39: 487-492Crossref PubMed Scopus (44) Google Scholar Beyond the growth factors and immunoglobulins likely contained within this colostrum protein concentrate, even the amino acid composition of the diet has been an important area of investigation. Investigations into the effect of arginine supplementation following intestinal resection has yielded conflicting results, with recent reports indicating that enteral L-arginine inhibits structural aspects of intestinal adaptation in the rat.41Sukhotnik I. Lerner A. Sabo E. Krausz M.M. Siplovich L. Coran A.G. Mogilner J. Shiloni E. Effects of enteral arginine supplementation on the structural intestinal adaptation in a rat model of short bowel syndrome.Dig Dis Sci. 2003; 48: 1346-1351Crossref PubMed Scopus (17) Google Scholar Contemporary nutritional recommendations for intestinal rehabilitation include consumption of 30 g/day oral glutamine42Wilmore D.W. Indications for specific therapy in the rehabilitation of patients with the short-bowel syndrome.Best Pract Res Clin Gastroenterol. 2003; 17: 895-906Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar; however, the literature regarding the stimulatory effects of glutamine will be reviewed by Dr Alpers within this supplement.Among digestible carbohydrates, Weser et al43Weser E. Babbitt J. Hoban M. Vandeventer A. Intestinal adaptation. Different growth responses to disaccharides compared with monosaccharides in rat small bowel.Gastroenterology. 1986; 91: 1521-1527PubMed Google Scholar demonstrated that disaccharides are more trophic to the rat small bowel than monosaccharides. Data such as these led to the hypothesis that it is the “functional workload” induced in the epithelium, whereby the need for hydrolytic digestion and absorption of nutrients within the lumen serves as an important stimulus for intestinal adaptation. Indeed, isotonic luminal infusions of nonmetabolizable substances requiring act
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