A Central Role for Lipocalin-2 in the Adaptation to Short-Bowel Syndrome Through Down-Regulation of IL22 in Mice.

BACKGROUND & AIMS: In short-bowel syndrome (SBS), inadequate intestinal adaptation is responsible for the majority of complications, including sepsis, liver failure, and death. In this study, we sought to further delineate the adaptive response to identify potential therapeutic targets. METHODS: We performed a 75% small-bowel resection (SBR) or sham operation on C57Bl/6J wild-type (WT), lipocalin-2 (LCN2)-/-, and interleukin 22 (IL22)-/- mice. Exogenous IL22 was administered to SBR WT mice. Cecal fecal matter from SBR WT and SBR LCN2-/- mice were transplanted into germ-free mice. Intestinal permeability, inflammation, proliferation, and the microbiome were evaluated 1 week after surgery. CD4+IL22+ laminal propria lymphocytes were sorted by flow cytometry. Naïve T cells were polarized to T-helper cells with or without LCN2. RESULTS: A 75% SBR in a mouse re-creates the increased intestinal permeability, enterocyte proliferation, and intestinal dysbiosis seen in SBS. LCN2 expression increases after 75% SBR, and this increase can be abrogated with broad-spectrum antibiotic treatment. LCN2-/- mice have less intestinal inflammation, increased IL22 expression, and greater adaptation as evidenced by less intestinal permeability, increased carbohydrate enzyme expression, less weight loss, and less dysbiosis after 75% SBR than WT mice. The proinflammatory and anti-adaptive effects of LCN2 can be transferred to germ-free mice via a fecal transplant. Administration of exogenous IL22 improves adaptation and restores the normal microbiome after 75% SBR in WT mice. CONCLUSIONS: LCN2 promotes inflammation and slows intestinal adaptation through changes in the microbiome and IL22 inhibition in a mouse SBS model. Strategies to reduce LCN2 may offer novel therapeutic approaches to enhance adaptation in SBS.

An exclusive human milk diet for very low birth weight newborns-A cost-effectiveness and EVPI study for Germany.

OBJECTIVES: Human milk-based fortifiers have shown a protective effect on major complications for very low birth weight newborns. The current study aimed to estimate the cost-effectiveness of an exclusive human milk diet (EHMD) compared to the current approach using cow's milk-based fortifiers in very low birth weight newborns. METHODS: A decision tree model using the health states of necrotising enterocolitis (NEC), sepsis, NEC + sepsis and no complication was used to calculate the cost-effectiveness of an EHMD. For each health state, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (RoP) and neurodevelopmental problems were included as possible complications; additionally, short-bowel syndrome (SBS) was included as a complication for surgical treatment of NEC. The model was stratified into birth weight categories. Costs for inpatient treatment and long-term consequences were considered from a third party payer perspective for the reference year 2017. Deterministic and probabilistic sensitivity analyses were performed, including a societal perspective, discounting rate and all input parameter-values. RESULTS: In the base case, the EHMD was estimated to be cost-effective compared to the current nutrition for very low birth weight newborns with an incremental cost-effectiveness ratio (ICER) of €28,325 per Life-Year-Gained (LYG). From a societal perspective, the ICER is €27,494/LYG using a friction cost approach and €16,112/LYG using a human capital approach. Deterministic sensitivity analyses demonstrated that the estimate was robust against changes in the input parameters and probabilistic sensitivity analysis suggested that the probability EHMD was cost-effective at a threshold of €45,790/LYG was 94.8 percent. CONCLUSION: Adopting EHMD as the standard approach to nutrition is a cost-effective intervention for very low birth weight newborns in Germany.

Bile salt dependent lipase promotes intestinal adaptation in rats with massive small bowel resection.

Intestinal adaptation is important for the short bowel syndrome (SBS) patients. Growing evidence has suggested that bile salt dependent lipase (BSDL) not only has the lipolytic activity, but also the immune-modulating and pro-proliferative activities. The purpose of the present study was to investigate the effects of BSDL on intestinal adaptive growth and gut barrier function in a rat model of SBS. Twenty-four male Sprague-Dawley rats were randomly divided into three experimental groups: sham group (rats underwent bowel transection and re-anastomosis), SBS group (rats underwent 80% bowel resection), SBS-BSDL group (SBS rats orally administered BSDL). The animals were weighed daily. The intestinal morpho-histochemical changes and intestinal barrier function were determined 14 days after the operations. Meanwhile, the expressions of Wnt signaling molecules in enterocytes were also analyzed by immunohistochemistry and Western blot. The postoperative weight gain was faster in the SBS rats treated with BSDL than in the SBS/untreated group. The SBS rats treated with BSDL had significantly greater villus height, crypt depth, and enterocyte proliferation in their residual intestines, as compared with the SBS/untreated group. The recovery of intestinal barrier function was promoted and the expressions of tight-junction proteins were increased in the SBS rats treated with BSDL. Additionally, the data indicated that the proadaptive activities of BSDL might be mediated by Wnt signaling activation in the enterocytes. These observations suggested that enteral BSDL administration promoted intestinal adaptive growth and barrier repairing by activating Wnt signaling pathway in SBS rats.

The impact of intestinal resection on the immune function of short bowel syndrome patients.

Short bowel syndrome (SBS) is characterized by a massive intestinal loss after surgery resection. Likewise, disturbances involving the intestine, which represents a complex immune environment, may result in breakdown of homeostasis and altered responses, thus leading to unpredictable clinical outcomes. However, the consequences of bowel resection were poorly investigated until now. Therefore, this study aimed to evaluate the immunological status of SBS-patients. For this purpose, ten subjects and nine healthy controls were evaluated. Along with some metabolic disturbances, the main results showed higher levels of the inflammatory cytokine IL-6 in plasma among SBS-patients. However, there were no differences in the frequency of CD3+, CD3+CD4+ or CD3+CD8+ T lymphocytes. An augmented frequency in CD4+ and CD8+ cells producing IFN-γ was also observed in peripheral blood mononuclear cells (PBMC), together with elevated percentage of CD4+ cells producing IL-10. No differences were observed in the frequency of total CD4+CD25-, CD4+CD25+ lymphocytes nor in the expression of FoxP3 or GITR. Nevertheless, SBS-patients showed higher frequency of the regulatory T cell population CD4+CD25+CD39+ cells in PBMC. In conclusion, these data pointed to SBS as an important disturbance that compromises not only the intestinal environment but also negatively influences systemic immune components.

Increased Anti-Flagellin and Anti-Lipopolysaccharide Immunoglobulins in Pediatric Intestinal Failure: Associations With Fever and Central Line-Associated Bloodstream Infections.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) pose a significant challenge in the lives of patients with intestinal failure (IF). We hypothesized that plasma immunoglobulins against flagellin (FLiC) and lipopolysaccharide (LPS) would be able to differentiate CLABSIs from nonbacterial febrile episodes and that levels would increase with infection and decline following appropriate antibiotic treatment. MATERIALS AND METHODS: Patients with IF, due to short bowel syndrome, between the ages of 3 months and 4 years of age, were recruited at Cincinnati Children's Hospital Medical Center. Anti-FLiC and anti-LPS plasma antibody levels were measured in 13 children with IF at baseline, during febrile events, and also following treatment with antibiotics. These were also measured in 11 healthy children without IF who were recruited as controls. RESULTS: Plasma anti-FLiC IgA levels increased during febrile episodes in all patients with IF (baseline mean of 1.10 vs febrile episode mean of 1.32 optical density units, respectively; P = .046). Neither plasma anti-FLiC nor anti-LPS IgA or IgG levels distinguished CLABSI from nonbacterial febrile episodes compared with baseline levels. Compared with controls, patients with IF had significantly higher plasma levels of anti-FLiC and anti-LPS IgA at baseline. CONCLUSION: Plasma anti-FLiC IgA antibody levels rise during febrile episodes but do not differentiate between nonbacterial febrile illnesses and CLABSIs in pediatric IF. However, the upregulation of these antibodies in IF suggests the baseline systemic presence of Gram-negative bacterial products.

Updates on acute and chronic rejection in small bowel and multivisceral allografts.

PURPOSE OF REVIEW: The surgical management of short bowel syndrome now includes intestinal (ITx) and multivisceral transplantation (MVTx), which has advanced and is now a sustainable option for the treatment of intestinal failure. Improvements in immunosuppressive therapies, excellence in surgical and medical management and enhanced post-transplant monitoring have all contributed to optimizing this solid organ transplant as a means of supplanting the diseased native bowel and alimentary tract with a functional alternative. RECENT FINDINGS: Post-transplant management is a critical and challenging phase of gastrointestinal transplantation, and the transplant pathologist is an essential member of the transplant team who identifies many of the early and late complications after ITx and MVTx. Among the most injurious and common complications of ITx and MVTx is acute rejection and, to a lesser degree, chronic rejection. Both of these broad categories of rejection are principally identified by histopathological changes in the allograft; however, biomarkers and other laboratory analytes are rapidly evolving into critical ancillary tools in identifying and further characterizing the rejection process. Thus, the transplant pathologist must also be able to utilize numerous other laboratory tests and panels of molecular biomarkers that provide supplementary information to accompany the biopsy interpretation and clinical suspicion of rejection. SUMMARY: Using biopsies and an assortment of additional approaches, the transplant pathologist is now able to provide swift and detailed information regarding the rejection process in the gastrointestinal transplant. This enables the clinical team to properly and successfully intercede, contributing to enhanced patient and graft survival.

Jejunoileal bypass as the main procedure in the onset of immune-related conditions: the model of BADAS.

Bariatric surgery represents a common approach for the control of severe morbid obesity, reducing caloric intake by modifying the anatomy of the gastrointestinal tract. Following jejunoileal bypass, a large spectrum of complications has been described, with rheumatic manifestation present in up to 20% of cases. Although bowel bypass syndrome, also called blind loop syndrome, is a well-recognized complication of jejunoileal bypass, the same syndrome was recognized in patients who had not had intestinal bypass surgery, and the term the 'bowel-associated dermatosis-arthritis syndrome' (BADAS) was coined. The pathogenesis of BADAS is as yet poorly understood and only few data concerning this issue have been published in the literature. The aim of the present paper is to review the literature and to discuss putative pathogenic mechanisms of BADAS, focusing on the immune system.

Potential benefits of pro- and prebiotics on intestinal mucosal immunity and intestinal barrier in short bowel syndrome.

The mechanism of impaired gut barrier function in patients with short bowel syndrome (SBS) is poorly understood and includes decreased intestinal motility leading to bacterial overgrowth, a reduction in gut-associated lymphoid tissue following the loss of intestinal length, inhibition of mucosal immunity of the small intestine by intravenous total parental nutrition, and changes in intestinal permeability to macromolecules. Novel therapeutic strategies (i.e. nutritive and surgical) have been introduced in order to prevent the establishment or improve the outcome of this prevalent disease. Pre- and probiotics as a nutritive supplement are already known to be very active in the intestinal tract (mainly in the colon) by maintaining a healthy gut microflora and influencing metabolic, trophic and protective mechanisms, such as the production of SCFA which influence epithelial cell metabolism, turnover and apoptosis. Probiotics have been recommended for patients suffering from SBS in order to decrease bacterial overgrowth and prevent bacterial translocation, two major mechanisms in the pathogenesis of SBS. The present review discusses the research available in the international literature, clinical and experimental, regarding probiotic supplementation for this complicated group of patients based on the clinical spectrum and pathophysiological aspects of the syndrome. The clinical data that were collected for the purposes of the present review suggest that it is difficult to correctly characterise probiotics as a preventive or therapeutic measure. It is very challenging after all to examine the relationship of the bacterial flora, the intestinal barrier and the probiotics as, according to the latest knowledge, demonstrate an interesting interaction.

NOD2 gene polymorphism rs2066844 associates with need for combined liver-intestine transplantation in children with short-gut syndrome.

OBJECTIVES: The nucleotide-binding oligomerization protein 2 (NOD2) gene single nucleotide polymorphisms (SNPs) associated with Crohn's disease were recently associated with severe rejection after small-bowel transplantation (SBTx). The purpose of this study was to re-test this association and explore whether deficient innate immunity suggested by the NOD2 SNPs predisposes to intestine failure requiring isolated SBTx or combined liver-intestine failure requiring combined liver-SBTx (LSBTx). METHODS: Archived DNA from 85 children with primary isolated SBTx or LSBTx was genotyped with Taqman biallelic discrimination assays. To minimize confounding effects of racial differences in minor allele frequencies (MAFs), allelic associations were tested in 60 Caucasian recipients (discovery cohort). Replication was sought in an independent cohort of 39 Caucasian pediatric and adult SBTx patients. RESULTS: MAF for rs2066845 and rs2066847 was similar to that seen in 538 healthy North American Caucasians. In the discovery cohort, MAF for rs2066844 was significantly higher in LSBTx (13.5 vs. 3.6%, P=0.0007, Fisher's exact test), but not in isolated SBTx recipients (2.2 vs. 3.6%, P=NS), when compared with 538 healthy Caucasians. In addition, among LSBTx recipients who received identical immunosuppression, the minor allele of rs2066844 associated with early rejection in linear regression analysis (P=0.028) (all but one of the risk alleles were found in rejectors), decreased survival (P=0.015, log-rank, Kaplan-Meier analysis), and a 20-fold greater hazard of septic death in proportional hazard analysis (P=0.030). Steroid-resistant (severe) rejection and graft loss were associated with isolated SBTx (P=0.036 and 0.082, respectively), but not with NOD2 SNPs. The association between rs2066844 and combined liver-intestine failure requiring LSBTx was significant in the replication cohort (P=0.014), and achieved greater significance in the combined cohort (P=0.00006). CONCLUSIONS: The NOD2 SNP rs2066844 associates with combined liver and intestinal failure in subjects with short-gut syndrome, who require combined liver-intestine transplantation, and secondarily with early rejection and septic deaths.

Development of Crohn's disease in patients with intestinal failure: a role for bacteria?

We present 3 cases of Crohn's disease that developed in patients with previously diagnosed short bowel syndrome from another cause. There are characteristics unique to patients with short bowel syndrome that may increase their likelihood to develop Crohn's disease, based on current concepts of the pathophysiology of inflammatory bowel disease. These patients may have a higher than average prevalence of small intestinal bacterial overgrowth. This may lead to an increase in bacterial translocation and dysregulation of the intestinal immune response. In addition, these patients often require parenteral nutrition (PN) because of macronutrient and micronutrient deficiencies. Some patients receiving PN, particularly those with bowel obstructions, may be at risk for septicemia due to bacterial translocation. It is thought that PN may enhance intestinal dysmotility and impair gut immunity, contributing further to an antigenic immune response in the intestinal immune system, although supporting data is lacking. Finally, studies have demonstrated that patient's with Crohn's disease have a shorter bowel length before any intestinal resections and not related to disease activity. Although the significance of this is unclear, a shorter bowel length may potentially predispose people to the development of Crohn's disease via an alteration of intestinal motility and intestinal flora.

How immunocompromised are short bowel patients receiving home parenteral nutrition? Apropos a case of disseminated Fusarium oxysporum sepsis.

BACKGROUND: Catheter-related sepsis is the most frequent complication in patients receiving home parenteral nutrition (HPN) for short bowel syndrome (SBS). A low-grade systemic inflammatory state and an altered mucosal immune response, as well as diminished intestinal barrier function have been characterized in these patients. The possibility of systemic immunocompromise has only recently been suggested. CASE DESCRIPTION: A 45-year-old female with traumatic SBS was admitted for possible catheter-related sepsis. She was asplenic and had insulin-dependent diabetes mellitus as a result of a pancreatic resection. A large skin ulceration was present on her left calf, which appeared unusual for a disseminated bacterial infection. Chest x-ray and computed tomography scan revealed multiple subpleural pulmonary infiltrates consistent with bacterial or fungal dissemination. Blood cultures from the port system and from the peripheral blood grew Staphylococcus haemolyticus and Fusarium oxysporum. The port system was removed, and flucloxacillin and voriconazole were given for 33 and 35 days, respectively. Clinical signs of disseminated sepsis resolved slowly. Bone marrow biopsy ruled out primary hematologic disease. CONCLUSIONS: (1) Catheter-related sepsis in patients on HPN is usually caused by Gram-positive or Gram-negative bacteria or by Candida species. Identification of molds in blood cultures strongly suggests Fusarium species, which should be treated appropriately with voriconazole or amphotericin B. (2) HPN and SBS aggravated by asplenism and diabetes mellitus can cause severe immunocompromise. (3) Fusaria have a strong tendency to persist or reappear after bone marrow transplantation, which is therefore relatively contraindicated in these patients.

[Small bowel transplantation: Report of a single case]. / Primer trasplante de intestino en Chile: Caso clínico.

Small bowel transplantation is associated with a patient survival at one and five years, of 80% and 63%, respectively. We report a 36 year-old female with short bowel syndrome, subjected to the first small bowel transplantation performed in Chile. A cadaveric gran was used. Immunosuppression was achieved by means of alemtuzumab, tacrolimus, sirolimus, micofenolate mofetil and steroids. Serial endoscopies and biopsies were performed during seven months after transplantation. The most important late complications were a drug induced renal failure, infections caused by opportunistic agents and a gastrointestinal bleeding probably induced by drugs. After 29 months of follow up, the patient is ambulatory, on oral diet only and with no evidence of graft rejection.

Primer trasplante de intestino en Chile: Caso clínico / Small bowel transplantation: Report of a single case

Small bowel transplantation is associated with a patient survival atone and five years, of 80% and 63%, respectively. We report a 36 year-old female with short bowel syndrome, subjected to the first small bowel transplantation performed in Chile. A cadaveric graft was used. Immunosuppression was achieved by means of alemtuzumab, tacrolimus, sirolimus, micofenolate mofetil and steroids. Serial endoscopies and biopsies were performed during sevenmonths after transplantation. The most important late complications were a drug induced renal failure, infections caused by opportunistic agents and a gastrointestinal bleeding probably induced by drugs. After 29 months of follow up, the patient is ambulatory, on oral diet only, and with no evidence of graft rejection.

Dietary glutamine and oral antibiotics each improve indexes of gut barrier function in rat short bowel syndrome.

Short bowel syndrome (SBS) is associated with gut barrier dysfunction. We examined effects of dietary glutamine (GLN) or oral antibiotics (ABX) on indexes of gut barrier function in a rat model of SBS. Adult rats underwent a 60% distal small bowel + proximal colonic resection (RX) or bowel transection (TX; control). Rats were pair fed diets with or without l-GLN for 20 days after operation. Oral ABX (neomycin, metronidazole, and polymyxin B) were given in some RX rats fed control diet. Stool secretory immunoglobulin A (sIgA) was measured serially. On day 21, mesenteric lymph nodes (MLN) were cultured for gram-negative bacteria. IgA-positive plasma cells in jejunum, stool levels of flagellin- and lipopolysaccharide (LPS)-specific sIgA, and serum total, anti-flagellin- and anti-LPS IgG levels were determined. RX caused gram-negative bacterial translocation to MLN, increased serum total and anti-LPS IgG and increased stool total sIgA. After RX, dietary GLN tended to blunt bacterial translocation to MLN (-29%, P = NS) and significantly decreased anti-LPS IgG levels in serum, increased both stool and jejunal mucosal sIgA and increased stool anti-LPS-specific IgA. Oral ABX eliminated RX-induced bacterial translocation, significantly decreased total and anti-LPS IgG levels in serum, significantly decreased stool total IgA and increased stool LPS-specific IgA. Partial small bowel-colonic resection in rats is associated with gram-negative bacterial translocation from the gut and a concomitant adaptive immune response to LPS. These indexes of gut barrier dysfunction are ameliorated or blunted by administration of dietary GLN or oral ABX, respectively. Dietary GLN upregulates small bowel sIgA in this model.

Oral antibiotics attenuate bowel segment reversal-induced alterations in subpopulation and function of peripheral blood leukocytes, thymocytes, and splenocytes in massive bowel-resected rats.

BACKGROUND: The authors previously demonstrated that oral antibiotics significantly attenuated inflammatory response, improved intestinal bacterial overgrowth, and augmented anabolic response in massive bowel-resected rats with bowel-segment reversal. Herein, the effects of oral antibiotics on immune functions were investigated. METHODS: Male Wistar rats were subjected to a sham operation or a 70% small bowel resection with or without a 3-cm small bowel segment reversal. Thereafter, half numbers of animals with bowel resection and reversal were orally administered clindamycin plus amoxicillin (50 plus 50 mg/kg/day) for 3 weeks. Age-matched nonsurgical rats were included as references. Peripheral blood, spleen, and thymus were collected for analyzing immunocyte subpopulations and function. RESULTS: Bowel resection significantly decreased weight gain, thymic weight, and splenic helper-T, suppressor-T, and mature-B cells but significantly increased splenic macrophage distribution and concanvavalin A-stimulated splenocytic proliferation and cytokine production, such as tumor-necrosis factor (TNF)-alpha, interferon-gamma, and interleukin (IL)-2 (1-way ANOVA, P<.05). Bowel segment reversal further decreased circulating suppressor-T cells but increased circulating natural killer cells and spontaneous splenocytic TNF-alpha production. Segment reversal-induced elevations in bacterial numbers of gut content, circulating white blood cell, nitric oxide, IL-6, splenocytic interferon-gamma and IL-2 production, reductions in T-thymocytic distribution, and alterations in thymocytic interferon-gamma and IL-2 production were attenuated by oral antibiotics. Moreover, oral antibiotics significantly increased splenocytic granulocytes and spontaneous thymocytic proliferation. CONCLUSIONS: Oral antibiotics might augment the beneficial effects of bowel segment reversal on anabolism via attenuating bacterial overgrowth and inflammatory response, and restore subpopulation and function of splenocytes and thymocytes in massive bowel-resected rats.

Detectable serum flagellin and lipopolysaccharide and upregulated anti-flagellin and lipopolysaccharide immunoglobulins in human short bowel syndrome.

Gut barrier dysfunction may occur in short bowel syndrome (SBS). We hypothesized that systemic exposure to flagellin and lipopolysaccharide (LPS) in SBS might regulate specific immune responses. We analyzed serial serum samples obtained from parenteral nutrition (PN)-dependent patients with SBS versus non-SBS control serum. Serum from 23 adult SBS patients was obtained at baseline and 4, 8, 12, 16, 20, and 24 wk in a trial of modified diet with or without growth hormone. Control serum was obtained from 48 healthy adults and 37 adults requiring PN during critical illness. Serum flagellin was detected by an ELISA recognizing an array of gram-negative flagellins, and LPS was detected by limulus assay. Serum flagellin- and LPS-specific immunoglobulin levels (IgM, IgA, and IgG) were determined by ELISA. Serum flagellin and LPS were undetectable in control subjects. In contrast, serum flagellin, LPS, or both were detected in 14 SBS patients (61%) during one or more time points [flagellin alone, 5/23 (22%); LPS alone, 6/23 (26%); or flagellin + LPS, 3/23 (13%)]. Flagellin-specific serum IgM, IgA, and IgG levels were markedly increased in SBS patients compared with both control populations and remained elevated during the 6-mo study period. LPS-specific IgA was significantly higher in SBS patients compared with healthy controls; LPS-specific IgM, IgA, and IgG levels each decreased over time in association with PN weaning. We conclude that adults with PN-dependent SBS are systemically exposed to flagellin and LPS, presumably from the gut lumen. This likely regulates innate and adaptive immune responses to these specific bacterial products.

Frequent IgE sensitization to latex, cow's milk, and egg in children with short bowel syndrome.

Children with short bowel syndrome (SBS) undergo frequent operations, so they are at risk for sensitizing to latex. There have been isolated reports of sensitization to food in these children. In a cross-sectional study, we assessed sensitization to latex, cow's milk, and egg with skin prick tests (SPT) and serum-specific immunoglobulin E (IgE) in 14 children with SBS. Data were collected about the number of operations with latex devices, serum total IgE, and history of feeding with milk formula. Ten children were sensitized to latex (specific IgE median: 6.7 kU/l, range: 0.5-33). Compared with those non-sensitized, sensitized children had significantly (p < 0.05) higher levels of serum total IgE in z-units (mean rank 3.25 vs. 9.2, respectively), and more operations with latex devices (mean rank 3.75 vs. 9). Eight children were sensitized to cow's milk, one with only positive SPT, the other seven with serum-specific IgE (median: 3.5, range: 0.5-21.1 kU/l), and five to egg (specific IgE median: 0.68, range: 0.58-2.17 kU/l). Except for some isolated days with cow's milk formula, the children had been initially fed with a diet without intact cow's milk proteins. Sensitization to latex, cow's milk, and egg is very frequent in children with SBS. They should be treated in a latex-free environment since the very early stages of the disease, and should be routinely studied regarding food sensitization, as this might contribute as an added factor in the chronic diarrhea of these patients.

Immunonutritional effects during synbiotics therapy in pediatric patients with short bowel syndrome.

The aim of this study was to evaluate the effects of synbiotic therapy in patients with short bowel syndrome (SBS). Four pediatric patients with SBS, who were receiving synbiotics therapy including Bifidobacterium breve, Lactobacillus casei and galactooligosaccharides, were enrolled in this study. We evaluated changes in immunonutritional parameters before and after receiving synbiotics therapy. Four normal, healthy, age-matched children were enrolled as controls. Fecal samples from patients and controls were collected and analyzed for fecal bacterial flora and organic acid (OA) contents. Levels of short chain fatty acids (SCFA) such as butyrate, propionate, and acetate increased in one patient, and SCFA/total OA levels increased in three patients. Serum lymphocyte counts and concentrations of pre-albumin increased after beginning synbiotics therapy, reaching a statistically significant level at the ninth month compared to the pre-treatment level. There was an increasing trend in height and weight gain velocity during the study compared with the pre-treatment period. The patients' fecal bacterial flora improved as a result of synbiotics therapy. Synbiotics therapy may be very effective at improving the intestinal flora and systemic immunonutritional status of patients with SBS.