Parenteral nutrition and intestinal transplantation, essential clinical interventions for short bowel syndrome (SBS) patients, are limited by various complications such as impaired intestinal barrier, metabolic disorder, catheter-associated infection, and allogenic rejection, leading to inferior therapeutic outcomes. Here, inspired by the camel hump, an ingestible magnetic capsule (IMC) consisting of thermosensitive hydrogel microparticles (MPs) based on poly(N-isopropylacrylamide) and acrylamide and a magnetic shell made of NdFeB and polyvinyl alcohol is proposed to enable circular nutrition storage and supply to optimize enteral nutrition for SBS treatment. Thermosensitive hydrogel MPs absorb excessive fluid and subsequently release nutrients in response to the heat generated by the photothermal effect of the magnetic shell under near-infrared irradiation. IMC can be localized and retained in the small intestine by the attraction between the magnetic shell and the external ferromagnet. In a SBS rat model, consistent nutrition optimization significantly relieves the weight loss, improves the nutrition-related serological markers, and facilitates the adaptation of the remnant small intestinal epithelium. This study offers a proof of principle for the use of ingestible capsules for nutrient storage and supply, providing a potential strategy for SBS treatment.

To identify the prognostic factors for pediatric severe intestinal motility disorder (IMD).

We reviewed the medical records of patients with severe IMD, who required total parenteral nutrition (TPN) for ≥ 60 days at our institution between April, 1984 and March, 2023, examining their characteristics to identify prognostic factors.

The types of IMD in the 14 patients enrolled in this study were as follows: isolated hypoganglionosis (IHG, n = 6), extensive aganglionosis (EAG: n = 6), and chronic idiopathic intestinal pseudo-obstruction (CIIP, n = 2). There was no significant difference in mortality among the three types of severe IMD. Weaning-off TPN and the use of the colon were not significant prognostic factors, but cholestasis was a significant prognostic factor (p = 0.005). There was a high mortality rate (50%), with the major causes of death being intestinal failure-associated liver disease (IFALD) following hepatic failure, and catheter-related blood stream infection (CRBSI). One IHG patient underwent small bowel transplantation but died of acute rejection.

Severe IMD is still associated with a high mortality rate and cholestasis predicts the prognosis. Thus, preventing or improving IFALD and CRBSI caused by long-term TPN is important for reducing the mortality rate.

Intestinal failure-associated liver disease (IFALD) is a relatively common complication in individuals receiving parenteral nutrition (PN). IFALD can be manifested as different types of liver injury, including steatosis, cholestasis, and fibrosis, and could result in liver failure in some cases. The onset and progression of IFALD are highly dependent on various patient and PN-related risk factors. Despite still being under investigation, several mechanisms have been proposed. Liver injury can originate due to caloric overload, nutrient deficiency, and toxicity, as well as phytosterol content, and omega-6 to omega-3 fatty acids ratio contained in lipid emulsions. Additional mechanisms include immature or defective bile acid metabolism, acute heart failure, infections, and sepsis exerting negative effects via Toll-like receptor 4 and nuclear factor κB inflammatory signaling. Furthermore, lack of enteral feeding, gut dysbiosis, and altered enterohepatic circulation that affect the farnesoid x receptor-fibroblast growth factor 19 axis can also contribute to IFALD. Various best practices can be adopted to minimize the risk of developing IFALD, such as prevention and management of central line infections and sepsis, preservation of intestine's length, a switch to oral and enteral feeding, cyclic PN, avoidance of overfeeding and soybean oil-based lipid formulations, and avoiding hepatotoxic substances. The present review thus provides a comprehensive overview of all relevant aspects inherent to IFALD. Further research focused on clinical observations, translational models, and advanced toxicological knowledge frameworks is needed to gain more insight into the molecular pathogenesis of hepatotoxicity, reduce IFALD incidence, and encourage the safe use of PN.

Extensive resection of the small intestine leads to the development of short bowel syndrome (SBS), which reduces the effective absorptive surface area of the intestine and predisposes patients to emaciation, malnutrition, and other severe symptoms. Herein, green tea catechin (-)-epigallocatechin gallate (EGCG) and ferrous ions (Fe²⁺ ) are utilized to construct a nutrient carrier platform that self-assembles with nutrients to form phenolic-based nutrient complexes (PNCs). PNCs effectively prolong the residence and absorption time of nutrients in the intestine. Further this platform is applied to integrate full nutrient formula, an enteral nutrition (EN) preparation containing a range of full nutrient components. In an SBS rat model, the prepared phenolic-based integrative nutrient complexes (PINCs) enhance nutritional status, improve anemia and immune function, as well as facilitate the growth of remaining intestinal villi and crypts, and maintain the integrity of the intestinal barrier. In addition, PINCs enable the modulation of gut microbial dysbiosis, enrich the abundance of beneficial bacteria, and have no toxic effects after the long-term ingestion. These results provide a proof of principle for the use of polyphenol-based nanocomplexes as EN preparation, offering a feasible strategy for both nutritional support and therapeutic perspectives for SBS treatment.

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.

Short bowel syndrome is a harmful condition that needs experimental research.

To assess the impact of the ileocecal valve removal in a model of short bowel syndrome, in order to investigate the evolution of the colon under this circumstance.

Fifteen Wistar rats were equitable divided into: Control (Sham), Group I (70% enterectomy preserving ileocecal valve) and Group II (70% enterectomy excluding ileocecal valve). After enterectomy was performed jejunoileal or jejunocecal anastomosis and sacrificed the animals on 30th postoperative day for histomorphometric study of the colon. During this period, was observed the clinical evolution of the animals weekly including body weight measurement.

Group I and II presented progressive loss of weight. In Group I was observed diarrhea, perineal hyperemia and purple color of the colon during autopsy. Histomorphometry assay showed hypertrophy and hyperplasia of colon mucosa in Group I. In Group II the colon wall was thicker due to hypertrophy and muscular hyperplasia, and in mucosa vascular proliferation and inflammatory infiltrate were intense.

This short bowel syndrome model is relevant and achieve 100% of survival. Animal's weight loss was not altered by the presence or exclusion of the ileocecal valve. Animals with 70% of small bowel removal and presence of the ileocecal valve attained a better clinical evolution and histological colon adaptation than those without ileocecal valve.

Short bowel syndrome (SBS) is a dramatic clinical condition in both children and adults; the residual bowel length is not sufficient to avoid intestinal failure, with subsequent malnutrition and growth retardation, and intravenous support is required to provide the nutrients normally coming from the intestine. Apart from the primary disease, the medical status can be worsened by complications of intestinal failure: if there are irreversible, the prognosis is poor unless a successful intestinal rehabilitation is achieved. Areas covered: The rescue of the remnant small bowel requires a multidisciplinary expertise to achieve digestive autonomy. The use of intestinal trophic factors has shown encouraging results in improving the intestinal adaptation process. Whenever the residual bowel length is inadequate, in a well-selected population weaning parenteral nutrition (PN) off could be attempted by surgery through lengthening procedures. A further subset of patients, with total and irreversible intestinal failure and severe complications on PN, may have an indication to intestinal transplantation. This procedure is still affected by poor long-term results. Expert commentary: Novel approaches developed through a multidisciplinary team work, such as manipulation of microbiota or tissue bioengineering, should be added to current therapies to treat successfully SBS.

In Crohn disease, bowel-preserving surgery is necessary to prevent short bowel syndrome due to repeated operations. This study aimed to determine the remnant small bowel length cut-off and to evaluate the clinical factors related to nutritional status after small bowel resection in Crohn disease.We included 394 patients (69.3% male) who underwent small bowel resection for Crohn disease between 1991 and 2012. Patients who were classified as underweight (body mass index < 17.5) or at high risk of nutrition-related problems (modified nutritional risk index < 83.5) were regarded as having a poor nutritional status. Preliminary remnant small bowel length cut-offs were determined using receiver operating characteristic curves. Variables associated with poor nutritional status were assessed retrospectively using Student t tests, chi-squared tests, Fisher exact tests, and logistic regression analyses.The mean follow-up period was 52.9 months and the mean patient ages at the time of the last bowel surgery and last follow-up were 31.2 and 35.7 years, respectively. The mean remnant small bowel length was 331.8 cm. Forty-three patients (10.9%) underwent ileostomy, 309 (78.4%) underwent combined small bowel and colon resection, 111 (28.2%) had currently active disease, and 105 (26.6%) underwent at least 2 operations for recurrent disease. The mean body mass index and modified nutritional risk index were 20.6 and 100.8, respectively. The independent factors affecting underweight status were remnant small bowel length ≤240 cm (odds ratio: 4.84, P < 0.001), ileostomy (odds ratio: 4.70, P < 0.001), and currently active disease (odds ratio: 4.16, P < 0.001). The independent factors affecting high nutritional risk were remnant small bowel length ≤230 cm (odds ratio: 2.84, P = 0.012), presence of ileostomy (odds ratio: 3.36, P = 0.025), and currently active disease (odds ratio: 4.90, P < 0.001).Currently active disease, ileostomy, and remnant small bowel length ≤230 cm are risk factors affecting the poor nutritional status of patients with Crohn disease after small bowel resection.

Patients with intestinal failure (IF) and home parenteral nutrition commonly develop abnormal liver function tests. The presentations of IF-associated liver disease (IFALD) range from mild cholestasis or steatosis to cirrhosis and decompensated liver disease. We describe the reversal of IFALD in an adult patient with IF secondary to severe Crohn's disease and multiple small bowel resections. The patient developed liver dysfunction and pathology consistent with IFALD. Multiple causal factors were implicated, including nutrition-related factors, catheter sepsis and the use of hepatotoxic medications. Multidisciplinary treatment in a tertiary IF referral centre included aggressive sepsis management, discontinuation of hepatotoxic medications and a reduction of parenteral nutrition dependency through optimisation of enteral nutrition via distal enteral tube feeding. Upon this, liver function tests normalised.

Cholestatic liver disease consists of a variety of disorders. Primary sclerosing cholangitis and primary biliary cirrhosis are the most commonly recognized cholestatic liver disease in the adult population, while biliary atresia and Alagille syndrome are commonly recognized in the pediatric population. In infants, the causes are usually congenital or inherited. Even though jaundice is a hallmark of cholestasis, it is not always seen in adult patients with chronic liver disease. Patients can have "silent" progressive cholestatic liver disease for years prior to development of symptoms such as jaundice and pruritus. In this review, we will discuss some of the atypical causes of cholestatic liver disease such as benign recurrent intrahepatic cholestasis, progressive familial intrahepatic cholestasis, Alagille Syndrome, biliary atresia, total parenteral nutrition induced cholestasis and cholestasis secondary to drug induced liver injury.

Mucosal adaptation is an essential process in gut homeostasis. The intestinal mucosa adapts to a range of pathological conditions including starvation, short-gut syndrome, obesity, and bariatric surgery. Broadly, these adaptive functions can be grouped into proliferation and differentiation. These are influenced by diverse interactions with hormonal, immune, dietary, nervous, and mechanical stimuli. It seems likely that clinical outcomes can be improved by manipulating the physiology of adaptation. This review will summarize current understanding of the basic science surrounding adaptation, delineate the wide range of potential targets for therapeutic intervention, and discuss how these might be incorporated into an overall treatment plan. Deeper insight into the physiologic basis of adaptation will identify further targets for intervention to improve clinical outcomes.

It is unknown what feeding strategy to use during chemotherapy-induced gastrointestinal mucositis, which causes weight loss and possibly malabsorption. To study the absorptive capacity of amino acids during mucositis, we determined the plasma availability of enterally administered amino acids (AA), their utilization for protein synthesis, and the preferential side of the intestine for AA uptake in rats with and without methotrexate (MTX)-induced mucositis. Four days after injection with MTX (60 mg/kg) or saline (controls), rats received a primed, continuous dual-isotope infusion (intraduodenal and intravenous) of labeled L-leucine, L-lysine, L-phenylalanine, L-threonine, and L-methionine. We collected blood samples, assessed jejunal histology, and determined labeled AA incorporation in proximal and distal small intestinal mucosa, plasma albumin, liver, and thigh muscle. MTX-induced mucositis was confirmed by histology. The median systemic availability of all AA except for leucine was similar in MTX-treated rats and in controls. However, the individual availability of all AA differed substantially within the group of MTX-treated rats, ranging from severely reduced (<10% of intake) to not different from controls (>40% of intake in 5 of 9 rats). More AA originating from basolateral uptake than those originating from apical uptake were used for intestinal protein synthesis in MTX-treated rats (≥420% more, P < 0.05). We conclude that continuous enteral administration can enable normal AA absorption in rats with MTX-induced mucositis. The intestine prefers basolateral AA uptake to meet its need for AA for protein synthesis during mucositis.

Patients with chemotherapy-induced gastrointestinal mucositis often suffer from weight loss. It is not well known how to enterally feed mucositis patients, potentially experiencing malabsorption. Recently, we showed in a rat model of methotrexate (MTX)-induced mucositis that intestinal absorption of glucose in trace amounts is still intact. We now determined the quantitative capacity to absorb glucose in rats with mucositis, relative to controls.

We administered a physiologically relevant amount of [1-(13)C]glucose-enriched glucose (meal size) as a bolus by oral gavage (2 g/kg once) or continuously by intraduodenal infusion (±1.9 g/(kg·h) for 5 h) to rats with MTX-induced mucositis and controls. Blood [1-(13)C]glucose concentrations were determined during the experimental period. To calculate the quantitative absorptive capacity, Steele's one-compartment model, including simultaneous intravenous infusion of [6,6-(2)H(2)]glucose, was used. After the experiment, jejunal histology and plasma citrulline concentrations were assessed.

MTX-induced mucositis was confirmed by a reduction in villus length and plasma citrulline (both -57%, relative to controls, P < 0.01). When glucose was administered as a bolus, MTX-treated rats only absorbed 15% of administered glucose, compared with 85% in controls (medians, P < 0.01). Upon continuous intraduodenal glucose infusion, the median absorptive capacity for glucose in MTX-treated rats did not differ from controls (80 versus 93% of administered glucose respectively, P = 0.06). However, glucose absorption differed substantially between individual MTX-treated rats (range, 21-95%), which correlated poorly with villus length (rho = 0.54, P = 0.030) and plasma citrulline (rho = 0.56, P = 0.024).

Continuous enteral administration can almost completely overcome the reduced absorptive capacity for glucose in rats with mucositis.

Short bowel syndrome (SBS) is a rare and severe condition where home parenteral nutrition (HPN) dependence can be either permanent or transient. The timing of HPN discontinuation and the survival, according to SBS characteristics, need to be further reported to help plan pre-emptive intestinal transplantation and reconstructive surgery.

268 Non-malignant SBS patients have been followed in our institution since 1980. HPN dependence and survival rate were studied with univariate and multivariate analysis.

Median follow-up was 4.4 (0.3-24) years. Actuarial HPN dependence probabilities were 74%, 64% and 48% at 1, 2 and 5 years, respectively. In multivariate analysis, HPN dependence was significantly decreased with an early (<6 mo) plasma citrulline concentration >20 μmol/l, a remaining colon >57% (4/7) and a remnant small bowel length >75 cm. Among the 124 patients who became HPN independent, 26.5% did so more than 2 years after SBS constitution.

This study indicates that long-term HPN is required in 47% of SBS patients started on this therapy. HPN independence is significantly associated with the remnant small bowel length, remaining colon and early plasma citrulline concentration. Noteworthy, HPN dependence could be reversed until 5 years after SBS constitution.

Studies on the long-term effects of short bowel syndrome (SBS) on the quality of life are scarce. Therefore, we determined health-related quality of life (HRQoL) in children and adolescents with a history of infantile SBS compared with that of same-aged controls drawn from the general population.

Cross-sectional assessment (2005-2007) of HRQoL in children with a history of infantile SBS treated in their first year of life, born between 1987 and 2002, using generic HRQoL measures was performed. Children aged 5 to 18 years and their parents filled out the Pediatric Quality of Life Inventory. Differences in scores between subjects and controls were analyzed using independent sample t tests.

Thirty-one children with a history of SBS (19 girls and 12 boys; mean age, 11.8 ± 4.2 years) participated, giving an overall response rate of 70%. The children and their parents reported significantly lower HRQoL than 275 healthy age-matched children and their parents (P < .05).

Children with a history of infantile SBS have a lower HRQoL than healthy age-matched controls. This difference lasts beyond childhood and way beyond the period of intestinal rehabilitation early in life. These findings highlight the need for targeted interventions to address these dimensions of impaired HRQoL.

Children with intestinal failure (IF) suffer from insufficient intestinal length or function, making them dependent on parenteral nutrition (PN) for growth and survival. PN and its components are associated with many complications ranging from simple electrolyte abnormalities to life-threatening PN-associated liver disease, which is also called intestinal failure-associated liver disease (IFALD). From a nutrition perspective, the ultimate goal is to provide adequate caloric requirements and make the transition from PN to full enteral nutrition (EN) successful. Upon review of the literature, we have summarized the most effective and innovative PN and EN therapies for this patient population. Antibiotic-coated catheters and antibiotic or ethanol locks can be implemented, as they appear effective in reducing catheter-related infection and thus further reduce the risk of IFALD. Lipid emulsions should be given judiciously. The use of an omega-3 fatty acid-based formulation should be considered in patients who develop IFALD. Trophic feeding is important for intestinal adaptation, and EN should be initiated early to help wean patients from PN. Long-term management of children with IF continues to be an emerging field. We have entered uncharted territory as more children survive complications of IF and IFALD. Careful monitoring and individualized management to ensure maintenance of growth while avoiding complications are the keys to successful patient outcomes.

Intestinal failure (IF) is the ultimate malabsorption state, with multiple causes, requiring long-term therapy with enteral or intravenous fluids and nutrient supplements. The primary goal during management of children with potentially reversible IF is to promote intestinal autonomy while supporting normal growth, nutrient status, and preventing complications from parenteral nutrition therapy. This article presents how an improved understanding of digestive pathophysiology is essential for diagnosis, successful management, and prevention of nutrient deficiencies in children with IF.

Short bowel syndrome (SBS) is a malabsorptive state occuring as a result of surgical resection or congenital disease of a significant portion of the small intestine . The amount of resection or remaining bowel generally dictates the degree of malabsorption and consequentely the need for specialized enteral nutrition or parenteral nutrition (PN). Intestinal failure in the context of SBS is defined as a dependence on PN to maintain minimal energy and fluid requirement for growth in children. Common causes of SBS in infants and children include necrotizing enterocolitis, midgut volvulus, intestinal atresia, and gastroschisis. Early identification of patients at risk for long-term PN dependency is the first step toward avoiding severe complications. Close monitoring of nutritional status, steady and early introduction of enteral nutrition, and aggressive prevention, diagnosis, and treatment of infections such as central venous catheter sepsis and bacterial overgrowth can significantly improve the prognosis. Intestinal transplantation is an emerging treatment that may be considered when intestinal failure is irreversible and children are experiencing serious complications related to TPN administration.

Using a massively bowel-resected rat model, our previous study demonstrated that small bowel segment reversal stimulates jejunal hyperplasia but may also increase the possibility of bacterial translocation and the elevation of circulating white blood cells and serum interleukin-6 that may reduce the whole-body anabolism. The aim of this study is to investigate whether oral antibiotics might attenuate the inflammatory responses and might therefore facilitate the beneficial effects of bowel segment reversal.

Male Wistar rats (approximately 270 g) underwent a 70% small bowel resection with (REV group) or without (CON group) a 3-cm small bowel segment reversal, or underwent a sham operation (SHAM group). After surgeries, half of the animals in the REV group were given oral clindamycin plus amoxicillin (50 plus 50 mg/kg/d, ANT group) for 3 weeks.

Oral antibiotics administration significantly attenuated the decreases in feeding efficiency (g of body weight/100 kcal diet) and increases in the circulation of white blood cells, serum nitric oxide, and interleukin-6 (1-way ANOVA, p < .05), which are associated with bowel segment reversal. In addition, antibiotics significantly increased serum concentrations of insulin-like growth factor-I, significantly decreased the total numbers of bacteria in the intestine, and tended to reduce the extent of jejunal hyperplasia in rats with bowel segment reversal.

Our results suggest that oral antibiotics may be used as an adjuvant to attenuate the inflammatory responses and to enhance the anabolic responses in massively bowel-resected patients with bowel segment reversal.

Sustained increases in mucosal surface area occur in remaining bowel following massive intestinal loss. The mechanisms responsible for expanding and perpetuating this response are not presently understood. We hypothesized that an increase in the number of intestinal stem cells (ISC) occurs following intestinal resection and is an important component of the adaptive response in mice. This was assessed in the jejunum of mice 2-3 days, 4-5 days, 6-7 days, 2 wk, 6 wk, and 16 wk following ileocecal resection (ICR) or sham operation. Changes in ISC following ICR compared with sham resulted in increased crypt fission and were assayed by 1) putative ISC population (SP) by flow cytometry, 2) Musashi-1 immunohistochemistry, and 3) bromodeoxyuridine (BrdU) label retention. Observed early increases in crypt depth and villus height were not sustained 16 wk following operation. In contrast, long-term increases in intestinal caliber and overall number of crypts per circumference appear to account for the enhanced mucosal surface area following ICR. Flow cytometry demonstrated that significant increases in SP cells occur within 2-3 days following resection. By 7 days, ICR resulted in marked increases in crypt fission and Musashi-1 immunohistochemistry staining. Separate label-retention studies confirmed a 20-fold increase in BrdU incorporation 6 wk following ICR, confirming an overall increase in the number of ISC. These studies support that expansion of ISC occurs following ICR, leading to an overall increase number of crypts through a process of fission and intestinal dilation. Understanding the mechanism expanding ISCs may provide important insight into management of intestinal failure.

The introduction of the Total Parenteral Nutrition (TPN) has given rise to a new hope in the treatment of intestinal failure (LF) associated with the Short Bowel Syndrome (SBS). However, together with the TPN and the increase of survival of these patients, new problems and questions have emerged, as well as new therapeutical procedures. Taking into consideration this emerging reality, this paper has the purpose to undertake a review of current concepts and available treatments for patients with IF associated-liver disease. Although TPN provides an increase of survival of patients with intestinal failure, it is a potential source of complication such as: septicemia, hyperglycemia, venous thrombosis and liver disease. There are several hypothesis conceived to explain the liver disease associated to intestinal failure, however the only definite treatment as a potential to reverse the non-cirrhotic liver disease is the small intestine transplantation. Despite indications for intestine transplantation are not entirely defined in literature, the trend is its early indication in high-risk patients, preserving the liver integrity and preventing the eventual need of both liver and intestine transplantations altogether.

Early intestinal adaptation after massive small bowel resection (SBR) is driven by increased epithelial cell (EC) proliferation. There is a clear clinical difference in the post-operative course of patients after the loss of proximal (P) compared to distal (D) small bowel. This study examined the effects of the site of SBR on post-resectional intestinal adaptation, and investigated the potential mechanisms involved. C57BL/6J mice (n = 7/group) underwent: (1) 60% P-SBR, (2) 60% D-SBR, (3) 60% mid (M)-SBR and (4) SHAM-operation (transection/reanastomosis). Mice were sacrificed at 7 days after surgery and ECs and adjacent mucosal lymphocytes (IELs) isolated. Adaptation was assessed in both jejunum and ileum by quantification of villus height, crypt depth, villus cell size, crypt cell size (microns), goblet cell number, and EC proliferation (%BrdU incorporation). Proliferation signalling pathways including keratinocyte growth factor (KGF)/KGFR(1), IL-7/IL-7R, and epidermal growth factor receptor (EGFR) were measured by RT-PCR. Expression of IL-7 was further analysed by immunofluorescence. Data were analyzed using ANOVA. All three SBR models led to significant increases in villus height, crypt depth, goblet cell numbers and EC proliferation rate when compared to respective SHAM groups. The strongest morphometric changes were found for jejunal segments after M-SBR and for ileal segments after P-SBR. Furthermore, morphometric analysis showed that at 1-week post-resection a tremendous increase in EC numbers occurred in jejunal villi (cell hyperplasia), whereas a significant increase in EC size predominated in ileal villi (cell hypertrophy). mRNA expression of KGF, KGFR(1), IL-7R, and EGFR showed a significant increase only after D-SBR, whereas IL-7 increased significantly after SBR in all investigated models, and this was confirmed by immunofluorescence studies. Early intestinal adaptation shows distinct differences depending on the site of SBR, and is predominately driven by cell hyperplasia in jejunal villi and cell hypertrophy in ileal villi. However, the exact mechanisms, which guide these signalling pathways are still unclear.

Short bowel syndrome (SBS) is defined in adults as a malabsorption disorder as a result of shortening the bowel to <200 cm. The severity of symptoms is less dependent on the amount of residual intestine than on the anatomical position of the resected bowel, the type of operative reconstruction, and the type and quality of nutritional, medical, and surgical treatment. Numerous complications and deficiency symptoms are associated with SBS. The extent of deficient nutrition should be determined. The need to create accesses for enteral and parenteral delivery, to supply supplementation as needed, perform pharmacological therapy, and in individual cases surgical treatment all necessitate a broad knowledge of nutritional medicine. The goals of therapy are correction and prevention of malnourishment, restoration of a normal nutritional status, and the normal thriving of children. Complications should be avoided, particularly those problems associated with parenteral nutrition. The frequency of diarrhea should be reduced. Overall, the aim is to achieve an optimized quality of life.

Short bowel syndrome (SBS) can lead to intestinal failure and require total or supplemental parenteral nutrition (TPN or PN, respectively). Glucagon-like peptide 2 (GLP-2) is a nutrient-dependent, proglucagon-derived gut hormone that stimulates intestinal adaptation.

Our objective was to determine whether supplemental enteral nutrients (SEN) modulate the intestinotrophic response to a low dose of GLP-2 coinfused with PN in a rat model of SBS (60% jejunoileal resection plus cecectomy).

Rats were randomly assigned to 8 treatments by using a 2 x 2 x 2 factorial design and maintained with either TPN or PN for 7 d. The 3 main treatment effects were the following: transection or resection (TPN alone), +/- SEN (days 4-6), and +/- GLP-2 (100 mug . kg body wt(-1) . d(-1)).

The treatments induced differential growth of duodenal and jejunal mucosa. Significant differences in villus height, crypt depth, dry mass, and concentrations of protein and DNA were observed between the treatments and TPN alone (SEN: 15-59% increase; GLP-2: 14-84% increase; and SEN + GLP-2: 63-160% increase). Plasma concentrations of bioactive GLP-2 were significantly greater with GLP-2 infusion (TPN alone: 25 +/- 9 pmol/L; SEN: 29 +/- 10 pmol/L; GLP-2: 59 +/- 31 pmol/L; SEN + GLP-2: 246 +/- 40 pmol/L) and correlated with mucosal growth. Jejunal sucrase activity (in U/cm) was significantly greater with SEN than without SEN. SEN + GLP-2 induced dramatic mucosal growth and greater plasma concentration of GLP-2 (SEN x GLP-2 interaction, P < 0.0001). Resection significantly increased expression of proglucagon mRNA in colon.

Combination treatment with SEN and GLP-2 induced a synergistic response resulting in greater mucosal cellularity and digestive capacity in parenterally fed rats with SBS. This shows that SEN improve the intestinotrophic response to exogenous GLP-2, possibly by stimulating enterocyte proliferation and differentiation.