Necrotizing enterocolitis (NEC) represents a severe condition in infants, with perforation being a particularly critical pathological manifestation. However, there is an absence of guidelines regarding the refeeding of infants recovering from perforation subsequent to NEC. This study aimed to determine the optimal refeeding method for term infants recovering from perforation after NEC. The study encompassed three aspects: the timing of enteral nutrition (EN) resumption, the progression of EN, and the method of EN resumption. Ninety full-term neonates who developed perforation following NEC and underwent surgical intervention were included. These samples were divided into early enteral nutrition (EEN, < 7 days) and late enteral nutrition (LEN, ≥ 7 days) groups based on the timing of EN resumption; faster increase (FI, ≥ 20 ml/kg/d) and slower increase (SI, < 20 ml/kg/d) groups based on the progression of EN; intact protein formula (IPF), special medical formula (SMF, including EHF and AABF), and mixed feeding (MF) groups based on the method of EN resumption. EEN infants had a lower incidence of intestinal stenosis and reoperation (43.5% vs. 77.6%, p = 0.002; 60.9% vs. 82.1%, p = 0.038), and a shorter duration of hospital stay after surgery and parenteral nutrition (PN) than LEN infants (14 days vs. 20 days, p < 0.001; 11 days vs. 17 days, p < 0.001). Faster increasing feed volumes was associated with shorter duration of hospital stay and parenteral nutrition (15 days vs. 20 days, p < 0.001; 14 days vs. 17 days, p < 0.001), but a slower rate of weight gain (0.020 kg vs. 0.129 kg, p < 0.01). The time to repeat NPO in SMF group is shorter than IPF an MF groups (3 days vs. 4 days and 9 days, p = 0.025). Our study demonstrates the beneficial effects of early enteral feeding and fast advancement of feed volumes in term infants with NEC and perforation after surgery, specifically in reducing short-term complications and the duration of hospital stay following surgery and PN. Additionally, this study suggests that IPF and MF significantly contribute to stimulate intestinal adoption recovery.

Necrotizing enterocolitis (NEC) is a neonatal disease with high mortality and morbidity. There is a lack of evidence-based recommendations on nutritional rehabilitation following NEC, and much of the current practice is guided by institutional policies and expert opinions. After a diagnosis of NEC, infants are exposed to an extended period of bowel rest and a prolonged course of antibiotics. Recognizing the patient characteristics that predict nutritional tolerance, early initiation of enteral nutrition, minimizing periods of bowel rest and antibiotic exposure, and standardization of dietary practices are the mainstay of post-NEC nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Massive intestinal resection is a regrettably necessary but life-saving intervention for progressive or fulminant necrotizing enterocolitis (NEC). However, the resultant short bowel syndrome (SBS) poses its own array of challenges and complications. Within hours of such an abrupt loss of intestinal length, the intestine begins to adapt. Our ability to understand this process of intestinal adaptation has proven critical in our ability to clinically treat the challenging problem of short bowel syndrome. This review first highlights key data relating to intestinal adaptation including structural and functional changes, biochemical regulation, and other factors affecting the magnitude of intestinal adaptation responses. We then focus on intestinal rehabilitation as it relates to strategies to enhance intestinal adaptation while meeting nutritional needs and preventing complications of parenteral nutrition.

Short bowel syndrome (SBS) is a rare disease that results from extensive resection of the intestine. When the remaining absorption surface of the intestine cannot absorb enough macronutrients, micronutrients, and water, SBS results in intestinal failure (IF). Patients with SBS who suffer from IF require parenteral nutrition for survival, but long-term parenteral nutrition may lead to complications such as catheter sepsis and metabolic diseases. Spontaneous intestinal adaptation occurs weeks to months after resection, resulting in hyperplasia of the remnant gut, modification of gut hormone levels, dysbiosis, and hyperphagia. Oral nutrition and presence of the colon are two major positive drivers for this adaptation. This review aims to summarize the current knowledge of the mechanisms underlying spontaneous intestinal adaptation, particularly in response to modifications of luminal content, including nutrients. In the future, dietary manipulations could be used to treat SBS.

The optimal regimen for enteral nutritional support in the management of children with short bowel syndrome (SBS) is not well characterized. A high fat, enteral diet is theoretically beneficial due to increased caloric density and enhanced structural adaptation. We therefore sought to determine the long-term effects of a high fat diet (HFD) on liver injury, a common complication of SBS, compared to a standard chow (SC) diet.

Using a parenteral nutrition-independent model of resection-associated liver injury, C57BL/6 mice underwent a sham operation or a 50% or 75% proximal small bowel resection (SBR). Mice in each group were then fed either a HFD (35% kcal fat) or SC (13% kcal fat). At post-operative week 15, markers of liver injury were quantified.

Liver triglyceride levels were increased from 7- to 19-fold in mice on the HFD compared to mice fed SC in the sham, 50%, and 75% resection groups. Serum ALT (2.2-fold increase in 75% resected mice compared to sham controls) and AST (2.0- and 2.7-fold increases in 50% and 75% resected mice, respectively) levels as well as fibrotic liver staining were elevated only in resected mice fed a HFD.

Long-term enteral feeding of HFD in our murine SBS model is associated with hepatic steatosis and liver injury. Our observation that liver steatosis and injury occur independent of parenteral nutrition suggests that enteral feeding composition and magnitude of intestinal loss may make a significant contribution to intestinal failure-associated liver disease.

Intestinal failure is defined as a critical reduction of the gut mass or function, below the minimum needed to absorb nutrients and fluids. The ultimate goal in intestinal failure is to promote bowel adaptation and reach enteral autonomy while a healthy growth and development is maintained. The condition is heterogeneous and complex. Therefore, recommendations for the type and duration of parenteral, enteral, and oral nutrition are variable, with the child's age as an additional key factor. The aim of this review is to provide an overview of nutritional feeding strategies in this heterogeneous population. Different perspectives on nutritional management, nutrition and adaptation, and microbiome and nutrition will be discussed.

In children, short-bowel syndrome (SBS) accounts for two-thirds of the cases of intestinal failure, and motility disorders and congenital mucosal diarrheal disorders account for the remaining one-third. Children with SBS are supported primarily by parenteral nutrition, which is the single-most important therapy contributing to their improved prognosis. More than 90% of children with SBS who are cared for at experienced intestinal rehabilitation programs survive, and roughly 60% to 70% undergo intestinal adaptation and achieve full enteral autonomy. This article focuses on the predictors of pediatric intestinal adaptation and discusses the pathophysiology and clinical management of children with SBS.

This article summarizes the current and potential future nutritional approaches to stimulate adaptation in intestinal failure. Adaptation in this context usually refers to intestinal adaptation but also involves changes in whole body physiology as well as in eating/drinking behavior.

Adaptation largely depends on residual functional anatomy. Luminal exposure to complex nutrients is the most important trigger for intestinal adaptation. Enteral fat as well as enteral or parenteral short chain fatty acids have a specific stimulatory effect. Zinc and vitamin A status need to be optimized for adaptation to proceed and be maintained. In the context of maintaining sodium and water homeostasis, flushing the remnant intestine because of uncontrolled thirst/drinking must be avoided. Complications of nutritional care such as malnutrition, intestinal failure-associated liver disease, and recurrent line sepsis also need optimal management.

Stimulation by luminal nutrients as well as prophylaxis against and treatment of (nutritional) complications are the cornerstones of adaptation to the short bowel situation. Based on ample data from animal studies but only limited evidence in humans specific nutritional stimulators need to be studied more rigorously. As long as such data are missing they can be tried on an individual basis.

Enteral autonomy and freedom from parenteral nutrition dependency is the ultimate therapeutic goal in children with intestinal failure. This can be achieved following attainment of bowel adaptation in conditions such as short bowel syndrome. Enteral nutrition is a major therapeutic cornerstone in the management of children with intestinal failure. It promotes physiological development, bowel adaptation and enhances weaning from parenteral nutrition. The optimal method of delivery, type of nutrients, timing of initiation, promotion of feeds and transition to solid food in children with short bowel syndrome are debated. Lack of high quality human data hampers evidence based conclusions and impacts daily practices in the field. Clinical approaches and therapeutic decisions are regularly influenced by expert opinion and center practices. This review summarizes the physiological principles, medical evidence and practice recommendations on enteral nutrition approaches in short bowel syndrome and provides a practical framework for daily treatment of this unique group of patients. Oral and tube feeding, bolus and continuous feeding, type of nutrients, formulas, trace elements and solid food options are reviewed. Future collaborative multicenter, high quality clinical trials are needed to support enteral nutrition approaches in intestinal failure.

The ultimate goal in the treatment of short bowel syndrome is to wean patients off parenteral nutrition, by promoting intestinal adaptation. Intestinal adaptation is the natural compensatory process that occurs after small bowel resection. Stimulating the remaining bowel with enteral nutrition can enhance this process. Additionally, medication can be used to either reduce factors that complicate the adaptation process or to stimulate intestinal adaptation, such as antisecretory drugs and several growth factors. The aim of this review was to provide an overview of the best nutritional strategies and medication that best promote intestinal adaptation.

Intestinal failure (IF), due to short bowel syndrome (SBS), results from surgical resection of a major portion of the intestine, leading to reduced nutrient absorption and need for parenteral nutrition (PN). The incidence is highest in infants and relates to preterm birth, necrotizing enterocolitis, atresia, gastroschisis, volvulus, and aganglionosis. Patient outcomes have improved, but there is a need to develop new therapies for SBS and to understand intestinal adaptation after different diseases, resection types, and nutritional and pharmacological interventions. Animal studies are needed to carefully evaluate the cellular mechanisms, safety, and translational relevance of new procedures. Distal intestinal resection, without a functioning colon, results in the most severe complications and adaptation may depend on the age at resection (preterm, term, young, adult). Clinically relevant therapies have recently been suggested from studies in preterm and term PN-dependent SBS piglets, with or without a functional colon. Studies in rats and mice have specifically addressed the fundamental physiological processes underlying adaptation at the cellular level, such as regulation of mucosal proliferation, apoptosis, transport, and digestive enzyme expression, and easily allow exogenous or genetic manipulation of growth factors and their receptors (e.g., glucagon-like peptide 2, growth hormone, insulin-like growth factor 1, epidermal growth factor, keratinocyte growth factor). The greater size of rats, and especially young pigs, is an advantage for testing surgical procedures and nutritional interventions (e.g., PN, milk diets, long-/short-chain lipids, pre- and probiotics). Conversely, newborn pigs (preterm or term) and weanling rats provide better insights into the developmental aspects of treatment for SBS in infants owing to their immature intestines. The review shows that a balance among practical, economical, experimental, and ethical constraints will determine the choice of SBS model for each clinical or basic research question.

Intestinal adaptation is a natural compensatory process that occurs following extensive intestinal resection, whereby structural and functional changes in the intestine improve nutrient and fluid absorption in the remnant bowel. In animal studies, postresection structural adaptations include bowel lengthening and thickening and increases in villus height and crypt depth. Functional changes include increased nutrient transporter expression, accelerated crypt cell differentiation, and slowed transit time. In adult humans, data regarding adaptive changes are sparse, and the mechanisms underlying intestinal adaptation remain to be fully elucidated. Several factors influence the degree of intestinal adaptation that occurs post resection, including site and extent of resection, luminal stimulation with enteral nutrients, and intestinotrophic factors. Two intestinotrophic growth factors, the glucagon-like peptide 2 analog teduglutide and recombinant growth hormone (somatropin), are now approved for clinical use in patients with short bowel syndrome (SBS). Both agents enhance fluid absorption and decrease requirements for parenteral nutrition (PN) and/or intravenous fluid. Intestinal adaptation has been thought to be limited to the first 1-2 years following resection in humans. However, recent data suggest that a significant proportion of adult patients with SBS can achieve enteral autonomy, even after many years of PN dependence, particularly with trophic stimulation.

Short bowel syndrome (SBS) is an increasingly common condition encountered across neonatal intensive care units. Improvements in parenteral nutrition (PN), neonatal intensive care and surgical techniques, in addition to an improved understanding of SBS pathophysiology, have contributed in equal parts to the survival of this fragile subset of infants. Prevention of intestinal failure associated liver disease (IFALD) and promotion of intestinal adaptation are primary goals of all involved in the care of these patients. While enteral nutritional and pharmacological strategies are necessary to achieve these goals, there remains great variability in the application of therapeutic strategies in units that are not necessarily evidence-based.

A search of major English language medical databases (SCOPUS, Index Medicus, Medline, and the Cochrane database) was conducted for the key words short bowel syndrome, medical management, nutritional management and intestinal adaptation. All pharmacological and nutritional agents encountered in the literature search were classified based on their effects on absorptive capacity, intestinal adaptation and bowel motility that are the three major strategies employed in the management of SBS. The Oxford Center for Evidence-Based Medicine (CEBM) classification for levels of evidence was used to develop grades of clinical recommendation for each variable studied.

We reviewed various medications used and nutritional strategies included soluble fiber, enteral fat, glutamine, probiotics and sodium supplementation. Most interventions have scientific rationale but little evidence to support their role in the management of infant SBS. While some of these agents symptomatically improve diarrhea, they can adversely influence pancreatico-biliary function or actually impair intestinal adaptation. Surgical anatomy and liver function are two important variables that should determine the selection of pharmacological and nutritional interventions.

There is a paucity of research investigating optimal clinical practice in infant SBS and the little evidence available is consistently of lower quality, resulting in a wide variation of clinical practices among NICUs. Prospective trials should be encouraged to bridge the evidence gap between research and clinical practice to promote further progress in the field.

Short bowel syndrome (SBS) refers to the sum of the functional alterations that are the result of a critical reduction in the length of the intestine, which in the absence of adequate treatment, presents as chronic diarrhea, chronic dehydration, malnutrition, weight loss, nutriment and electrolyte deficiency, along with a failure to grow that is present with greater frequency during the neonatal period. The aim was to carry out a review of the literature encompassing the definition and the most frequent causes of SBS, together with an understanding of its physiopathology, prognostic factors, and treatment. An Internet search of PubMed articles was carried out for the existing information published over the last 20 years on SBS in children, using the keywords "short bowel syndrome". From a total of 784 potential articles, 82 articles were chosen for the literature review. The treatment of patients presenting with SBS is quite a challenge and therefore it is necessary to establish multidisciplinary management with a focus on maintaining optimal nutritional support that covers the necessities of growth and development and at the same time provides a maximum reduction of short, medium, and long-term complications. The diagnosis and treatment of a child with SBS require a team of professionals that are experts in gastroenterologic, pediatric, and nutritional management. The outcome for the child will be directly related to opportune management, as well as to the length of the intestinal resection and the presence or absence of the ileocecal valve.

Intestinal failure (IF) affects a growing number of children due to increasing numbers of preterm infants surviving intestinal resection for necrotising enterocolitis and improving surgical techniques for congenital gut anomalies. Parenteral nutrition (PN) is the mainstay of therapy; enteral nutrition may have trophic effects on the gut.

To review systematically evidence for the effectiveness of medical and nutritional interventions in the treatment of IF in children.

Retrieval of data from studies of patients aged <18 years and receiving >28 days of PN. Outcome measures were improvement in intestinal function, intestinal adaptation, growth, prevention and treatment of IF-associated liver disease, and mortality. Cochrane Database (November 2009), MEDLINE (1950-November 2009) and CINAHL (1982-November 2009) electronic database searches were made using keyword and subject headings (MeSH): IF, Short Bowel Syndrome (SBS), PN and Child. The level of the evidence (EL) was assessed using SIGN (Scottish Intercollegiate Guidelines Network) methodology (http://www.sign.ac.uk).

From 1 607 620 hits, 720 abstracts were reviewed. Thirty-three original articles were included. No studies were of high methodological quality.

The evidence base for medical and nutritional interventions in paediatric IF is limited and of poor quality. In the absence of randomised-controlled trials, this evidence base can improve through case control and cohort research; and with better multiagency communication, the study of inter-centre differences is possible. Achievable short-term goals would include the study of: optimal ursodeoxycholic usage, novel intralipid formulations, cycled enteral antibiotics, enteral probiotics and new enteral feeding strategies.

Long chain polyunsaturated fatty acids (LCPUFA)seem to be the most trophic macronutrients in inducing intestinal adaptation in adult short bowel syndrome (SBS), although their effects on intestinal adaptation in infants with SBS remain unknown.It is hypothesized that a high fat diet enriched with n-3 LCPUFA derived from fish oil (FO) will increase intestinal adaptation compared with a diet dominated by n-6 PUFA from corn oil (CO) in weanling SBS rats after massive ileocecal resection (ICR). Twenty-day-old rats were sorted into four groups, CO-sham, FO-sham,CO-ICR, and FO-ICR groups, and fed ad lib with the CO or FO diet, respectively, for 7 d after sham or ICR surgery. Compared with CO-ICR rats, FO-ICR rats consumed less diet per gram of weight gain, had less diarrhea and fecal fat excretion, and demonstrated a tendency toward better weight gain. The mucosal mass, DNA and RNA levels of the colon and RNA levels of the distal jejunum, and the colonic mucosal area (%) were significantly higher in FO-ICR rats than in CO-ICR rats. These results suggest that the beneficial effect of dietary FO is associated with better adaptation in the colon in weanling rats after ICR.

Short bowel syndrome (SBS) is used to describe a condition of malabsorption and malnutrition resulting from the loss of absorptive area following massive small bowel resection. The key to improved clinical outcome after massive small bowel resection is the ability of the residual bowel to adapt. Although still in experimental stages, a major goal in the management of SBS may be the augmented use of growth factors to promote increased adaptation. A number of growth factors have been implicated in promoting the adaptation process. The best-described growth factors are reviewed: glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF), and growth hormone (GH). This article reviews the ability of recombinant GLP-2, EGF and GH to modulate structural and functional aspects of intestinal adaptation following small bowel resection. Although these growth factors have shown promise, small sample size, inconsistent measurement parameters and uncontrolled study designs have hampered the acquisition of strong data advocating the use of growth factor treatment for SBS. Multicenter trials using well-defined outcome measures to assess clinical efficacy are needed to direct the clinical indications, timing and duration of therapy and assess potential risks associated with growth factor therapies.

Short bowel syndrome occurs when there is insufficient length of the small intestine to maintain adequate nutrition and/or hydration status without supplemental support. This syndrome most frequently occurs following extensive surgical resection of the intestine, and the extent of adaptation depends on the anatomy of the resected bowel and the amount of bowel remaining. Following resection, the intestinal tissue undergoes morphologic and functional changes to compensate for the lost function of the resected bowel. These changes are mediated by multiple interactive factors, including intraluminal and parenteral nutrients, gastrointestinal secretions, hormones, cytokines, and growth factors, many of which have been well characterized in animal models. The amount of small bowel remaining is the most important predictor of adaptive potential; neither structural nor functional adaptative changes have been demonstrated in humans or animal models with more extreme resections resulting in an end-jejunostomy. The current understanding of these processes has led to the recent use of supplemental hormones, such as growth hormone and glucagon-like peptide 2, in intestinal rehabilitation programs and may lead to the development of pharmacologic agents designed to augment the innate adaptive response.

Intestinal failure (IF) can be defined as the reduction of functional gut mass below the minimal amount necessary for digestion and absorption adequate to satisfy the nutrient and fluid requirements for maintenance in adults or growth in children. In developed countries, IF mainly includes individuals with the congenital or early onset of conditions requiring protracted or indefinite parenteral nutrition (PN). Short bowel syndrome was the first commonly recognized cause of protracted IF. The normal physiologic process of intestinal adaptation after extensive resection usually allows for recovery of sufficient intestinal function within weeks to months. During this time, patients can be sustained on parenteral nutrition. Only a few children have permanent intestinal insufficiency and life-long dependency on PN. Non-transplant surgery including small bowel tapering and lengthening may allow weaning from PN in some cases. Hormonal therapy with recombinant human growth hormone has produced poor results while therapy with glucagon-like peptide-2 holds promise. Congenital diseases of enterocyte development such as microvillus inclusion disease or intestinal epithelial dysplasia cause permanent IF for which no curative medical treatment is currently available. Severe and extensive motility disorders such as total or subtotal intestinal aganglionosis (long segment Hirschsprung disease) or chronic intestinal pseudo-obstruction syndrome may also cause permanent IF. PN and home-PN remain are the mainstays of therapy regardless of the cause of IF. Some patients develop complications while receiving long-term PN for IF especially catheter related complications (thrombosis, sepsis) and liver disease. These patients may be candidates for intestinal transplantation. This review discusses the causes of irreversible IF and emphasizes the specific medico-surgical strategies for prevention and treatment of these conditions at several stages of IF.

Intestinal epithelial cell turnover (proliferation, migration, differentiation, and apoptosis) and gut barrier functions are dynamic processes that are markedly affected by nutritional status, the route of feeding, and the adequacy of specific nutrients in the diet. Emerging studies are defining potential therapeutic roles for specific nutrients and diet-derived compounds (including arginine, glutamate, glutamine, glutathione, glycine, vitamin A, zinc, and specific lipids) in gut mucosal turnover, repair, adaptation after massive bowel resection, and barrier function. The role and regulation of endogenous bowel flora in generating short-chain fatty acids from diet-derived fiber and other diet-derived compounds and the effects of these agents on gut function are increasingly being elucidated. Results of these investigations should define new nutritional methods for trophic and cytoprotective effects on the intestine in conditions such as inflammatory bowel disease, malnutrition, and short bowel syndrome.

The search for diets to improve the nutritive utilization of protein and magnesium in malabsorption syndrome led us to study goat milk, because of its particular nutritional characteristics, and to compare it with cow milk, which is most commonly consumed. We studied the nutritive utilization of protein and magnesium in transected rats (control) and in rats with resection of 50% of the distal small intestine. The diets used were the standard diet recommended by the American Institute of Nutrition and diets based on lyophilized goat or cow milk. The consumption of goat milk produces better protein efficiency ratio and food conversion efficiency values, particularly in rats with intestinal resection, together with a higher nutritive utilization of protein. Magnesium apparent digestibility coefficient is not modified by intestinal resection in rats fed with goat milk-based diet, on the contrary to the standard and cow milk diets. Magnesium apparent digestibility coefficient is greater for the goat milk group, which is reflected in the greater quantity of this mineral stored in bone. These results demonstrate the beneficial effect of goat milk on the nutritive utilization of protein and on magnesium bioavailability, especially in animals with resection of the distal small intestine.

Malabsorption of both nonessential and essential nutrients, fluid, and electrolytes will, if not compensated for by increased intake, lead to diminished body stores and to subclinical and eventually clinical deficiencies. By definition, intestinal failure prevails when parenteral support is necessary to maintain nutritional equilibrium. After intestinal resection, adaptation, a progressive recovery from the malabsorptive disorder, may be seen. Research has focused on optimizing remnant intestinal function through dietary or pharmacologic interventions. In this review, factors responsible for the morphologic and functional changes in the adaptive processes are described. Results of clinical trials employing either growth hormone and glutamine or glucagon-like peptide-2 in short bowel patients are presented.

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.

The nutritional support of gastrointestinal growth and function is an important consideration in the clinical care of neonatal infants. In most health infants, the provision of either breast milk or formula seems to support normal intestinal mucosal growth, but the most significant advantages of breast milk may be for host defense or gut barrier-related functions that are involved in reducing infection. The specific effects of various milk-borne growth factors on key mucosal immune and barrier functions are likely to provide valuable new clues to the advantages of human milk. A substantial number of preterm, low-birth weight babies or those suffering from compromised intestinal function, however, often cannot tolerate oral feedings and instead receive TPN. The consequences of TPN on gastrointestinal function and how this contributes to morbidity of these infants warrants further study, with respect to both clinical and basic research questions. Although enteral nutrition seems to be a critical stimulus for intestinal function, the minimal amounts and composition of nutrients necessary to maintain specific intestinal functions remain to be established. The experimental tools exist to start defining the specific nutrient requirements for the infant gut and some of these nutrients are known (e.g., glutamate, glutamine, and threonine). Peptide growth factors and gut hormones clearly play a role in gut growth and in several ways mediate the trophic actions of enteral nutrition. Although a number of these growth factors are good candidates for therapeutic use, their clinical application in the management of gastrointestinal insufficiency and disease has been slow. The emergence of GLP-2 as a trophic peptide that seems to target the gut is a promising candidate on the horizon.

Long chain polyunsaturated fatty acids (LCPUFAs) such as arachidonic acid (AA) and eicosapentaenoic acid (EPA) stimulate intestinal adaptation. Prostaglandins also enhance intestinal adaptation. The purpose of this study was to determine by which eicosanoid pathway dietary arachidonic acid enhances intestinal adaptation. Cyclo-oxygenase or lipoxygenase were selectively inhibited to determine whether either of them enhanced or inhibited adaptation.

Sixty Sprague-Dawley rats were divided into 2 groups, one receiving an 80% small bowel resection and the other receiving a sham operation. Rats were further divided into groups receiving either a placebo, a general lipoxygenase inhibitor (nordihydroguaiaretic acid [NDGA] at 40 mg/kg per day), or a cyclo-oxygenase-2 inhibitor (Etodolac at 3 mg/kg per day). Rats were pair-fed a diet containing 30% kcal from fat, primarily consisting of AA.

After 14 days, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining small intestine. There was a significant decrease in ileal mucosal mass in rats receiving Etodolac and a significant increase in mucosal mass in the duodenum in rats receiving NDGA (both p < .001). Mucosal DNA, protein, and disaccharidase data showed similar trends.

These findings suggest that after small bowel resection, dietary arachidonic acid may facilitate the adaptation process by acting as a substrate for the synthesis of prostaglandins, and not through the derivatives of lipoxygenase such as leukotrienes or thromboxanes.

To determine correlates of clinical outcomes in patients with short bowel syndrome (SBS).

Retrospective medical record review of neonates treated between 1986 and 1998 who met our criteria for SBS: dependence on parenteral nutrition (PN) for at least 90 days after surgical therapy for congenital or acquired intestinal diseases.

Thirty subjects with complete data were identified; 13 (43%) had necrotizing enterocolitis, and 17 (57%)had intestinal malformations. Mean (SD) residual small bowel length was 83 (67) cm. Enteral feeding with breastmilk (r = -0.821) or an amino acid-based formula (r = -0.793) was associated with a shorter duration of PN, as were longer residual small bowel length (r = -0.475) and percentage of calories received enterally at 6 weeks after surgery(r = -0.527). Shorter time without diverting ileostomy or colostomy (r = 0.400), enteral feeding with a protein hydrolysate formula (r = -0.476), and percentage of calories received enterally at 6 weeks after surgery (r = -0.504) were associated with a lower peak direct bilirubin concentration. Presence of an intact ileocecal valve and frequency of catheter-related infections were not significantly correlated with duration of PN. In multivariate analysis, only residual small bowel length was a significant independent predictor of duration of PN, and only less time with a diverting ostomy was an independent predictor of peak direct bilirubin concentration.

Although residual small bowel length remains an important predictor of duration of PN use in infants with SBS, other factors, such as use of breast milk or amino acid-based formula, may also play a role in intestinal adaptation. In addition, prompt restoration of intestinal continuity is associated with lowered risk of cholestatic liver disease. Early enteral feeding after surgery is associated both with reduced duration of PN and less cholestasis.

Enteral nutrition in pediatric short bowel syndrome is a key component in facilitating a child's growth and development. In addition, aggressive use of enteral nutrition is not only one of the most important factors in promoting intestinal adaptation; it as well avoids the numerous complications associated with long-term parenteral nutrition. This manuscript will review the appropriate enteral nutrition for a child with short bowel syndrome. Issues to be addressed include appropriate enteral formula selection, solid food intake, enteral administration routes, and devices. Information presented is based on current research as well as experience with a large population of pediatric short bowel syndrome patients.

Certain lipids, primarily long chain fatty acids and especially long chain polyunsaturated fatty acids (LCPUFAs) from marine oils, stimulate gut adaptation after resection. The goal of this study was to define the degree of resection that provides an optimal model for adaptation and to determine if dietary LCPUFAs improve intestinal adaptation after resection.

One hundred and fifty-g male Sprague-Dawley rats were divided into groups receiving 60%, 70%, and 80% bowel resection. After resection, each group was subdivided into two dietary groups and pair fed diets containing either safflower oil or docosahexaenoic acid (DHA) and arachidonic (AA).

After 2 weeks, mucosal mass, protein, DNA, and disaccharidase activity were measured in the remaining intestine. Rats receiving 80% resection responded with the highest level of intestinal adaptation. Within the 80% resection group, diet containing DHA and AA stimulated adaptation significantly more than safflower diet. A second study further evaluated the effect on LCPUFAs on intestinal adaptation. Diets included a control group 10% soy oil, and three diets differing in their AA-DHA fat blend ratio at 5% AA and 3.3% DHA, 15% AA and 10% DHA, and 45% AA and 30% DHA. The addition of LCPUFAs to diets enhanced intestinal adaptation in a linear, dose-dependent manner after an 80% small bowel resection. Rats fed a diet containing 30% DHA-45% AA had significantly enhanced mucosal mass compared to rats fed a diet containing 10% soy oil, and considerably higher compared to rats fed 3.3% DHA-5% AA.

These studies suggest that modification of dietary LCPUFAs may enhance intestinal adaptation in short bowel syndrome.

Certain nutrients and other trophic factors are highly sensitive stimulants of intestinal adaptation following short bowel syndrome. Growth hormone and glutamine in a modified diet have been shown to enhance nutrient absorption in patients with severe short bowel syndrome. However, neither growth hormone nor glutamine is capable of enhancing adaptation in an animal model. This study was conducted to determine if the combination of glutamine and growth hormone could enhance gut adaptation following massive small bowel resection in the rat.

Thirty-four male rats received 70% jejunoileal resection. The first group received glycine and rat growth hormone, the second glutamine and rat growth hormone, and the third glycine but no growth hormone.

There was no evidence that the combination of glutamine and growth hormone could enhance mucosal mass, mucosal protein, or mucosal DNA levels relative to the other two control groups of animals. Likewise, sucrase activities were not enhanced by glutamine and growth hormone.

It is unlikely that the combination of glutamine and growth hormone will be of benefit in the treatment of patients with short bowel syndrome. The results in previous human studies can be alternatively explained by the long-term nonspecific effect of enteral nutrition on gut adaptation.

This article discusses the management of short bowel syndrome from the time of intestinal resection until the patient either recovers free of supplemental parenteral and enteral nutrition or progresses to the point of needing intestinal transplantation. The importance of aggressive use of enteral feedings is emphasized, especially in relation to the process of intestinal adaptation. An approach to the various complications of short bowel syndrome, especially small bowel bacterial overgrowth, is discussed. Surgical options short of transplantation also are described. Intestinal transplantation and its present and future roles in the management of patients with short bowel syndrome are discussed.

Short bowel syndrome (SBS) in the newborn results in limited intestinal absorptive capacity, leading especially to fatty acid (FA) malabsorption. It is unknown whether adaptation occurs in time in FA absorption, and whether this adaptation is chain-length dependent. The aid of the present study was to prospectively evaluate FA absorption and excretion during SBS in the newborn. Twenty-one neonates who underwent small bowel resection (of variable length) for various reasons (necrotizing enterocolitis, intestinal atresia, meconium peritonitis, cloacal extrophy, etc) were studied. Eight neonates had SBS, defined as a small bowel remnant of less than 50% of the original small bowel length related to gestational age. The mean remaining small bowel length in the SBS group was 34% (24% to 42%). The non-SBS control group consisted of 13 neonates who had only minor small bowel resections. The mean remaining bowel length for the non-SBS group was 95% (70% to 100%). The results show that the total fractional excretion of FA (FE-FA) at 2 weeks and 1, 2, 3, and 4 months postsurgery was 51% +/- 37%, 33% +/- 24%, 51% +/- 65%, 53% +/- 27%, and 7% +/- 2% in patients with SBS, versus 12% +/- 8%, 24% +/- 10%, 9% +/- 3%, 8% +/- 3% and 17% +/- 14% in the non-SBS controls, respectively (P < .05 by ANOVA). There appeared to be an amelioration in time in FA absorption, especially in the SBS group, after 3 months. FE-FA was chain-length related, being considerably less for C10 and C12 than for C14 and longer amounts. An amelioration of absorption occurred in the SBS patients, especially with the longer-chain FA. On the basis of the study data, the authors conclude that in the initial adaptation phase shorter chain lengths are better absorbed than longer chain lengths; however, in the latter FA group, substantial adaptation occurs with time.

The effects of medium chain triglycerides (MCT) on jejunal mucosa mass and protein synthesis were compared with results from previous experiments with rats fed by parenteral nutrition or enteral nutrition. Other published studies have also been analysed. Three experimental models were studied. In the traumatic model, production of a femoral fracture was followed by Kirschner pin insertion into the medullary canal of both fragments at reduction. (Forty ras were fed enteral nutrition and 93 were given parenteral nutrition.) A second model entailed resection under ether anaesthesia using the technique described by Higgins. (Fifty five rats were fed enteral nutrition and 28 with parenteral nutrition.) A third model entailed a terminolateral portocaval shunt under anaesthesia with pentobarbital. (Sixty nine rats were treated this way and then given enteral nutrition.) Proportions of medium chain/long chain triglycerides (LCT) were as follows: 0/100, 20/80, 40/60, 50/50, and 92/8 for enteral nutrition and 0/100, 30/70, 50/50, and 70/30 for parenteral nutrition. Faecal losses of alpha amino nitrogen, protein, total fats, and free fatty acids were analysed together with the quantitative intake, weight gain of the rats, jejunal mucosal mass, and protein synthesis in relation to the MCT proportion ingested or given by enteral nutrition or parenteral nutrition. From analysis of our results and those of others, several conclusions could be drawn. Firstly, the route of administration of MCT is extremely important and enterocytes might be considered one of the main target sites. Secondly, a high proportion of MCT (more than 80%) offers no advantage for jejunal mucosa and produces undesirable side effects. Thirdly, the effect of MCT on jejunal mucosal protein synthesis depends on the metabolic state. Finally, an increase in jejunal mucosal mass directly correlated with MCT concentrations, but no correlation was found between mass and protein synthesis. A positive correlation, however, between MCT proportion and enzyme activity (alkaline phosphatase and sucrase) in the brush border membrane was seen as well as a positive correlation with the concentration of phospholipids in the microvilli.