Therapy For Short Bowel Syndrome Research Articles

An updated overview of glucagon-like peptide-2 analog trophic therapy for short bowel syndrome in adults.

Short bowel syndrome (SBS) is a clinical condition characterized by a failure to achieve optimal intestinal adaptation, which is necessary to maintain oral/enteral autonomy. At present, the treatment options for SBS are primarily intestinal replacement and rehabilitation. Intestinal rehabilitation mainly includes non-transplantation surgery and intestinal rehabilitation measures. In recent years, intestinal rehabilitation in patients with SBS using nutritional intestinal hormones, especially glucagon-like peptide-2 analogs, has made great progress. Many high-quality studies have provided evidence-based medical findings to support the development of clinical guidelines. This article reviews the latest research advancements regarding the use of glucagon-like peptide-2 analogs (teduglutide, glepaglutide, and apraglutide) in the treatment of SBS.

Enterohormone therapy for short bowel syndrome.

Short bowel syndrome (SBS) patients are at risk to develop intestinal failure when the decreased absorption of macronutrients, water, and electrolytes necessitates parenteral support for survival. The adverse effects of SBS and parenteral support negatively affect the quality of life (QoL) of SBS-intestinal failure patients. However, spontaneous intestinal adaptation along with disease-modifying therapies allow reducing parenteral support, thereby improving QoL. During the first years following extensive surgery, spontaneous structural and functional intestinal changes take place which stimulate a more efficient nutrient and fluid absorption in the remaining bowel. Given their potential role in the ileal braking mechanism, enterohormones, such as glucagon-like peptide (GLP)-2, GLP-1, and peptide YY (PYY), promote an accelerated adaptation or hyperadaptation. While the exact role of GLP-1 and PYY in SBS is still being explored, GLP-2 analogs have clearly shown to be effective in improving outcome in SBS. Whereas spontaneous intestinal adaptation improves the nutritional status of SBS patients to a certain extent, GLP-2 analogs can further decrease parenteral support needs through hyperadaptation. There are, however, other promising candidates on the horizon that - alone or in combination - could possibly establish additional disease-modifying effects.

Glucocorticoid Therapy in Short Bowel Syndrome: A New Fork in the Road?

Glucocorticoid Therapy in Short Bowel Syndrome: A New Fork in the Road?

The pivotal relation between glucagon-like peptides, NFκB and inflammatory bowel disease.

Glucagon-like peptides (GLPs), GLP-1 and GLP-2, are released from intestinal enteroendocrine cells (L cells) in response to ingested nutrients. GLP-1 plays a crucial role in lowering blood glucose and controlling body weight, through stimulating the islet ß cells of pancreas to secrete insulin, inhibiting gastric emptying, and reducing food ingestion. Therefore, GLP-1 receptor agonists are now used in the treatment of obese patients with type 2 diabetes mellitus (T2DM). GLP-2, on the other hand, is used as a novel therapy for short bowel syndrome (SBS) through its ability to restore intestinal homeostasis and induce epithelial proliferation. GLPs and the inhibitors of their degradation enzymes, dipeptidyl peptidase-IV (DPP-IV) inhibitors, have many anti-inflammatory actions. Many animal-based clinical trials have proved that GLP-based therapy has a pivotal role in the management of inflammatory bowel disease (IBD), possibly through regulating the transcription factor nuclear factor kappa-ligand B (NFκB). NFκB controls the production and secretion of many cytokines and chemokines encountered in the pathophysiology of IBD such as interleukin (IL-1β-IL-12, IL-13, IL-21, IL-22, IL-6) and tumour necrosis factor-alpha (TNF-α) and hence, may provide a promising therapeutic option.

PD41-03 MORE THAN 30 YEARS OF EXPERIENCE WITH THE ILEAL NEOBLADDER: FUNCTIONAL AND METABOLIC OUTCOMES

You have accessJournal of UrologyTrauma/Reconstruction/Diversion: Ureter (including Pyeloplasty) and Bladder Reconstruction (including fistula), Augmentation, Substitution, Diversion II (PD41)1 Apr 2020PD41-03 MORE THAN 30 YEARS OF EXPERIENCE WITH THE ILEAL NEOBLADDER: FUNCTIONAL AND METABOLIC OUTCOMES Bjoern Volkmer*, Kassel Germany, and Richard Hautmann Bjoern Volkmer*Bjoern Volkmer* More articles by this author , Kassel GermanyKassel Germany More articles by this author , and Richard HautmannRichard Hautmann More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000921.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The ileal neobladder (INB) has now been performed on a regular basis for more than 30 years at our institution. This study aims to assess the long term functional outcomes including near normal voiding function, continence, incidence of UTI and metabolic requirements. METHODS: From our consecutive series of 893 male patients who underwent radical cystectomy (RC) and urinary diversion with the INB from 1986 to 2009 we only included those with minimum follow-up of 5 years. We excluded patients with previous irradiation therapy of abdomen or pelvis, with previous other forms of urinary diversion, and with postoperative tumor recurrence. Between 10/08 and 03/09 questionnaires were sent to the remaining 303 patients, with telephone-interviews in those, who did not respond. 44 patients were not available: Death with NED in n=43, living abroad n=6, and n=5 with Alzheimer’s. The remaining 259 patients formed the study population. Continence was defined as use of not more than 1 pad/daytime or nighttime. Patients were asked for the number of feverish UTI within the last 5 years, problems with mucus production, and requirement of (self)catheterization. RESULTS: The mean age at the time of surgery was 60.6±10y ranging from 23y to 81y. The mean time of follow-up in this series was 131±56mon ranging from 60mon to 267mon. The mean age at the time of the survey was 73±10y ranging from 43y to 92y. While the risk of urinary retention and bicarbonate therapy decreased over time, the changes in the rate of daytime and nighttime incontinence seemed to be attributed more to age than to the length of follow-up (Table 1). Transurethral catheters were required in 1 case after 12, in 2 cases after 16 and 17 years postoperatively. Three patients are on substitution of vitamin B12, one patient is on colestyramine therapy for short bowel syndrome. One patient developed end stage renal failure 5 years after surgery. CONCLUSIONS: INB patients who survived more than 5 years after RC and diversion enjoy acceptable urinary continence and retain their ability to void spontaneously in >90 % of patients. The percentage of recurrent UTI and the need of bicarbonate therapy are not negligible. Especially in young patients with favourable pathologic findings an ileal neobladder provides excellent results even after 20 years and more. Source of Funding: None © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e821-e822 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Bjoern Volkmer* More articles by this author Kassel Germany More articles by this author Richard Hautmann More articles by this author Expand All Advertisement PDF downloadLoading ...

Exosomes-mediated Transfer of miR-125a/b in Cell-to-cell Communication: A Novel Mechanism of Genetic Exchange in the Intestinal Microenvironment.

Glucagon-like peptide-2 (GLP-2), a key factor in intestinal rehabilitation therapy of short bowel syndrome (SBS), may require cell-to-cell communication to exert its biological functions. However, understanding of the mechanism remains elusive. Here, we report participation of exosomal miR-125a/b in GLP-2 mediated intestinal epithelial cells-myofibroblasts cross-talk in intestinal microenvironment.Methods: The effects of GLP-2 on the proliferation and apoptosis of intestinal epithelial cells in SBS rat models were evaluated. Exosomes were extracted from residual jejunum tissue of GLP-2 or vehicle treated SBS rats using ultracentrifugation method, and identified by nanoparticle trafficking analysis (NTA), transmission electron microscopy and western blotting. miRNA sequencing combined with qRT-PCR validation were used to identify differentially expressed miRNAs. miRNAs, which might be involved in proliferation and apoptosis of intestinal epithelial cells, were screened and further verified by miRNA functional experiments. Moreover, the proliferation-promoting and anti-apoptosis effects of GLP-2 on intestinal myofibroblasts, which expressing GLP-2 receptor, and whether GLP-2 could influence the content of miRNAs in the derived exosomes were studied. The downstream pathways were explored by miRNA function recovery experiment, luciferase reporter assay, pull down experiment, knockdown and overexpression of target gene and other experiments based on the bioinformatics prediction of miRNA target gene.Results: GLP-2 significantly promoted intestinal growth, facilitated the proliferation of intestinal crypt epithelial cells and inhibited the apoptosis of intestinal villi epithelial cells in type II SBS rats. GLP-2 significantly down-regulated exosomal miR-125a/b both in residual jejunums derived exosomes and in exosomes secreted by GLP-2R positive cells. Exosomal miR-125a/b was responsible for GLP-2 mediated intestinal epithelial cells proliferation promotion and apoptosis attenuation. miR-125a/b inhibited the proliferation and promotes apoptosis of intestinal epithelial cells by suppressing the myeloid cell leukemia-1 (MCL1).Conclusions: miR-125a/b shuttled by intestinal myofibroblasts derived exosomes regulate the proliferation and apoptosis of intestinal epithelial cells. GLP-2 treatment significantly decreases the level of miR-125a/b in the exosomes of intestinal myofibroblasts. miR-125a/b modulates the proliferation and apoptosis of intestinal epithelial cells by targeting the 3'UTR region of MCL1. Hence, this study indicates a novel mechanism of genetic exchange between cells in intestinal microenvironment.

Optimization of In-Continuity Spring-Mediated Intestinal Lengthening

BackgroundSpring-mediated intestinal lengthening has been studied in numerous animal models to effectively achieve up to a 3-fold increase in length. In this study we are interested in optimizing this method of spring lengthening. MethodsJuvenile mini-Yucatan pigs underwent laparotomy for spring implantation. Springs were secured by plicating the intestine around the springs. In one set of experiments, varying degrees of plication were compared to determine the necessary narrowing needed to confine the spring. In another set of experiments, dissolvable sutures were used for the plication to allow for spontaneous spring passage postoperatively. Intestinal segments were retrieved and evaluated for lengthening and histological changes. ResultsPigs tolerated their diet advancement to a regular diet postoperatively. 10% plication resulted in a 1.3-fold increase in length, while 50% plication resulted in a 2.7-fold increase in length (p<0.05). At two months postoperatively, the majority of springs had safely passed out of the intestine. All lengthened intestine showed significant growth histologically. ConclusionsA 50% reduction in lumen diameter achieves optimal spring-mediated intestinal lengthening. Springs can safely pass out of the intestine, thus avoiding a second operation for spring removal. These results may be important in developing future therapies for short bowel syndrome. Level of evidenceLevel I experimental study.

PT01.2: ZP7570: A Novel GLP-1/GLP-2 Dual Acting Peptide with Potential as the Next Generation Therapy for Short Bowel Syndrome

PT01.2: ZP7570: A Novel GLP-1/GLP-2 Dual Acting Peptide with Potential as the Next Generation Therapy for Short Bowel Syndrome

Disease modifying therapy in short bowel syndrome: finally coming of age?

Disease modifying therapy in short bowel syndrome: finally coming of age?

Innovative Discharge Process for Families with Pediatric Short Bowel Syndrome: A Prospective Nonrandomized Trial.

Home parenteral nutrition (HPN) is a life-sustaining therapy for short bowel syndrome (SBS) and other severe digestive diseases, but complications are common. We evaluated a predischarge HPN hands-on training course to reduce complications in children with SBS, including hospital readmissions. We conducted a prospective, nonrandomized controlled research study between April 1, 2014, and April 30, 2017. Eligible participants were children aged <18 years old with SBS and anticipated HPN dependence duration ≥6 months. Excluded participants had a previous history of discharge with a central venous catheter (CVC), HPN, or intravenous fluids or strictly palliative goals of care. An intervention group practiced hands-on HPN within the hospital room for 24 hours using infusion equipment. The groups received standard teaching (CVC care, home infusion pump operation, HPN preparation and administration). Nine children were assigned to the intervention group and 12 served as controls. The median age was 8.4 months, and length of stay (LOS) was 82 days. All participants experienced ≥1 event, with a total of 47 issues related to HPN. There were no significant associations between group assignment and 30-day postdischarge events. Each additional week of LOS was associated with 11% increase in the odds of an emergency department visit (OR 1.11; 95% CI, 1.01-1.26) and 16% increase in the odds of readmission (OR 1.16; 95% CI, 1.04-1.37). Postdischarge events remained widespread despite HPN bedside interventions offered by this pilot intervention. With refinement of HPN discharge processes, quality benchmarks are needed.

Basic fibroblast growth factor eluting microspheres enhance distraction enterogenesis

PurposeThe purpose of this study was to determine if distraction enterogenesis using self-expanding polycaprolactone (PCL) springs is a potential therapy for short bowel syndrome. Sustained release basic fibroblast growth factor (bFGF) microspheres have been shown to induce angiogenesis and intestinal regeneration in tissue engineered scaffolds. We hypothesized that the provision of bFGF-loaded microspheres would increase angiogenesis and thereby enhance the process of enterogenesis. MethodsA 10-mm segment of rodent jejunum was isolated and an encapsulated PCL spring inserted. Blank or bFGF-loaded microspheres were delivered to the segment. After 4weeks, jejunal segments were assessed for lengthening, morphology, quantification of blood vessels, and ganglia. ResultsLengthened intestinal segments receiving bFGF microspheres demonstrated significantly increased microvascular density compared to those with blank microspheres. There were also significantly more submucosal and myenteric ganglia in the segments that received bFGF microspheres. Segments achieved similar lengthening and final muscular thickness in both blank and bFGF groups, but the bFGF microsphere caused a significant increase in luminal diameter of the jejunal segment. ConclusionSustained release bFGF microspheres enhanced distraction enterogenesis through improved vascularity. The synergy of growth factors such as bFGF with distraction enterogenesis may yield improved results for the future treatment of patients with short bowel syndrome.

Development of an endoluminal intestinal lengthening device using a geometric intestinal attachment approach

Distraction enterogenesis may provide a novel therapy for short bowel syndrome. Previously described methods have relied on isolated intestinal segments or transmural fixation because of ineffective endoluminal attachment. We hypothesized that a novel approach of geometric coupling between a tapering device and the mesenteric curvature would allow trans-stomal distraction enterogenesis. A catheter device was designed with tapering stiffness, consisting of a stiff catheter with a taper to a flexible latex tip to prevent perforation. Yorkshire pigs underwent creation of a jejunal Roux limb with device placed via jejunostomy. Intestinal attachment was achieved without a substantial decrease in bowel perfusion as measured by laser Doppler. An external clamp was secured at the stoma to provide external fixation of the device. The catheter was advanced 1cm/day for either 7 or 14days before explant. After 7days, the distracted segment achieved a mean±SD increase in length of 37±6% versus fed, nondistracted bowel, corresponding to an absolute gain of 10.6±1.7cm (1.5cm/day). After 14days, the Roux limb achieved an 80±2% increase in length versus fed control bowel, corresponding to an absolute gain of 16.8±3.0cm (1.2cm/day). No perforation or stoma-related complication occurred. We describe a novel catheter device with tapering stiffness allowing for endoluminal distraction enterogenesis via geometric coupling. This approach may allow development of clinically applicable technology for the treatment of patients with short bowel syndrome.

180. TARGT™ Shows Sustained Secretion of the Therapeutic Peptide GLP-2 Which Retains Functional Activity in SCID Mice and Rats

Glucagon-like peptide-2 (GLP-2) is a naturally occurring 33 amino acid peptide, with t1/2 of 6-7 min. This peptide is produced by L cells of small intestine and has several important functions, such as increasing intestinal absorption, stimulating intestinal growth, reducing bone breakdown and impacting gastric and intestinal motility. It is well known that individuals with short bowel syndrome benefit from exogenous GLP-2 to improve intestinal absorption.Native peptides have been difficult to develop into drugs because of their short half-life, poor metabolic stability and rapid clearance. Manufactured peptides frequently require structural modification and, long-acting formulations. Moreover, the treatment with such peptides frequently uses high doses, which can lead to off-target effects such as nausea and vomiting in some patients. As an alternative, we developed a novel approach that allows our TARGT™ (Transduced Autologous Restorative Gene Therapy) technology to produce and secrete peptides such as GLP-2.The TARGT™ system is an ex-vivo gene therapy, which we have now demonstrated is capable of providing autologous, continuous peptide therapies, at physiological ranges. Our group previously demonstrated such findings for certain proteins. In one set of experiments described herein, the TARGT™ system consists of several 2 × 30 mm biopsies of dermal tissue (Micro-Organ, MO), extracted under local anesthetic followed by fibroblast transduction with a Helper-Dependent Adenoviral Vector (HDAd) containing a novel GLP-2 gene expression cassette. After culture, and measurement of peptide production, one or more transduced MOs (TARGTs™) are re-implanted into the patient as required to achieve the desired dose. The system allows dose flexibility and the TARGTs™ may be added or removed according to in-vivo secretion levels.Pre-clinical studies, using this novel technology, showed GLP-2 TARGT (TARGTGLP-2) in-vitro secretion levels of tens of micrograms per day. Preliminary data from in-vivo SCID mice experiments confirms that TARGT-secreted human GLP-2 analog reaches the mouse blood stream and exhibits a sustained secretion profile similar to tho se observed and reported with other proteins using the TARGT™ technology (e.g. EPO, IFNα). In addition, in-vivo SCID mice and rat experiments suggest that TARGT™ secreted GLP-2 analog is active, and increases intestinal villous height and intestinal crypt cell proliferation rate.Data obtained so far suggests that TARGTGLP-2 may provide a favorable PK profile and physiologic levels of continuous GLP-2 for extended periods of time, avoiding supra-physiological peak serum concentration and achieving continuous coverage with less exposure compared to exogenous GLP-2 injections. The current results suggest that the TARGT™ platform is a promising novel therapy for short bowel syndrome and potentially other diseases of endogenous protein/peptide deficiency.

Animal models of gastrointestinal and liver diseases. Animal models of infant short bowel syndrome: translational relevance and challenges.

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.

A novel double-balloon catheter device for fully endoluminal intestinal lengthening.

Distraction enterogenesis may provide a novel therapy for short bowel syndrome (SBS). Previously described methods have relied upon isolated intestinal segments or transmural fixation. Our objective was to develop a novel, fully endoluminal device, permitting placement and removal through an enteral stoma or orifice. A flexible device was designed consisting of two latex balloons mounted on coaxial catheters. The inner catheter allowed longitudinal force transmission from an external spring. Yorkshire pigs underwent jejunal Roux limb creation with device placement via jejunostomy. Balloons were inflated to 52 mmHg without significant reduction in bowel perfusion as measured by laser Doppler. The device was explanted after 7 days. Distracted bowel achieved an increase in length of 26.1 ± 6.1 % vs nondistracted fed bowel. As the device resided in unfed bowel, a 66.7 ± 14.5% increase vs unfed bowel was noted. These corresponded to a gain of 6.3 ± 2.3 cm (0.9 ± 0.3 cm/day) and 12.9 ± 7.6 cm (1.8 ± 1.1 cm/day), respectively. Attachment sites demonstrated occasional epithelial sloughing with no balloon-associated perforation. A novel double-balloon catheter device allows for fully endoluminal distraction enterogenesis. This approach may allow development of clinically applicable technology for the treatment of patients with SBS.

Complex Dietary Protein Improves Growth Through a Complex Mechanism of Intestinal Peptide Absorption and Protein Digestion

The small intestinal epithelium has an impressive ability to adapt to changes resulting from loss of length or alteration in dietary load. We sought to determine the potential influence of dietary protein absorption on growth and development. We hypothesized that a complex protein diet would improve growth over that of an elemental diet. Using the nematode Caenorhabditis elegans, a transparent worm with a rudimentary intestinal tube lined by enterocytes that function remarkably similar to humans, we measured daily growth, intestinal peptide, and amino acid transporter expression and intestinal proteolysis to compare the effects of a complex protein diet to a diet containing only amino acids. Nematodes raised on a complex protein diet grew to adulthood faster than those raised solely on amino acids, which did not require an overall change in intestinal peptide or amino acid transporter expression. Despite no overall change in transporter expression, a shift in location of peptide transporter expression was noted between diets that corresponded to decreased rate of intestinal proteolysis seen in the complex protein-fed group. A complex protein diet stimulates in an altered pattern of intestinal peptide transporter expression and intestinal proteolytic activity that results in improved growth compared with a diet of elemental amino acids. This improved growth appears to be the result of increased efficiency of a smaller number of enterocytes. These data might be useful in targeting intestinal rehabilitation therapies for short bowel syndrome and other risk factors for intestinal failure.

Teduglutide: A Review of its Use in the Treatment of Patients with Short Bowel Syndrome

The recombinant analogue of human glucagon-like peptide-2 (GLP-2) teduglutide (Gattex(®), Revestive(®)) is a novel therapy for short bowel syndrome (SBS). GLP-2 is a naturally occurring hormone that regulates the growth, proliferation and maintenance of cells lining the gastrointestinal tract. Subcutaneous teduglutide is the first long-term medical therapy approved for the treatment of adult patients with SBS who are dependent on parenteral support (parenteral nutrition and/or intravenous fluids). In a pivotal, double-blind, multicentre, phase III study in adult patients with SBS who were dependent on parenteral support, a significantly higher proportion of teduglutide 0.05 mg/kg/day recipients than placebo recipients achieved at least a 20% reduction from baseline in weekly parenteral support volume at week 20 and maintained at week 24 (primary endpoint). The overall mean reduction in weekly parenteral support volume from baseline was greater in patients who received teduglutide compared with those who received placebo. Additionally, more teduglutide-treated patients achieved at least a one-day reduction in parenteral support than those receiving placebo. Subcutaneous teduglutide had an acceptable tolerability profile; the most frequently reported adverse events were of gastrointestinal origin, consistent with the underlying disease condition and the known mechanism of action of teduglutide.

Tu1976 Clostridium Butyricum Regulates IL-10 Production in Normal and Inflammatory Conditions Through Different Target Cells

Background: A shift in composition of intestinal microbiota is regarded to be important for the symptoms and complications of short bowel syndrome (SBS). However, attempts to normalize the colonic microbiota in SBS have not been formally studied. We investigated whether two weeks' treatment with Saccharomyces boulardii influences colonic microbiota and has an impact on the lactate levels in SBS patients. Methods: Symptoms and colonic microbiota were investigated in 14 SBS adult patients on long-term parenteral nutrition who were treated with Saccharomyces boulardii (Sb). A 250 mg capsule Sb was given twice daily for two weeks. Microbiota were investigated using structure functional fluorescence in situ hybridization (FISH) analysis of Carnoy fixated stool cylinders. Altogether 82 FISH probes representing different groups of microbiota were used. Stool samples were collected at days 0, 7, 14, as related to the start of Sb therapy. 10 healthy untreated persons were used as controls. Results: The patients had an apparently SBS-specific increase in the prevalence of Lactobacilli. Bacteroides (Bac303), Roseburia (EREC) groups increased, and Bifidobacteriaceae (Bac 164) and Enterobacteriaceae (Ebac) groups decreased significantly with Sb therapy in SBS. These changes all represented an alteration towards the distribution seen in the normal controls. The changes in all other microbial groups were not consistent, and the median values did not change significantly. The SBS-specific increase in Lactobacilli demonstrated a tendency to decrease, which was however statistically non-significant. However, probiotic treatment decreased levels of lactic acid from 30, 72 mg/dL to 18, 64 mg/dL, so to the reference value. Conclusions: The composition of colonic microbiota in patients with SBS on long term parenteral nutrition differs significantly from that in healthy persons. Saccharomyces boulardii treatment made the microbiota more similar to healthy controls. Especially strong effects are observed with regard to Bacteroides, Roseburia, Bifidobacteriaceae and Enterobacteriaceae groups. None of these bacterial groups showed complete normalization when compared to healthy controls however. The concentration of plasma lactate fell to reference values after Sb treatment. It is possible that the two-week treatment was insufficient to unravel specific shifts in other bacterial groups or to normalize the main fermentative groups. Longer-term therapeutic studies are necessary for what appears a promising strategy.

Ghrelin and glucagon-like peptide-2 increase immediately following massive small bowel resection

Children with short bowel syndrome face life-threatening complications. Therefore, there is an urgent need for a new therapy to induce effective adaptation of the remnant intestine. Adaptation occurs only during feeding. We focused on preprandial acyl ghrelin and des-acyl ghrelin, and postprandial glucagon-like peptide-2 (GLP-2), which are known to have active orexigenic and trophic actions. This study aims to clarify the secretion trends of these hormones after massive small bowel resection and to obtain basic data for developing a new treatment. Sixty-three growing male rats were used: 3 were designated as controls receiving no operation and 60 were randomized into the 80% small bowel resection (80% SBR) group and the transection and re-anastomosis group. Changes in body weight, food intake, and remnant intestine morphology were also assessed for 15 days after the operation. Acyl ghrelin and des-acyl ghrelin levels increased immediately, equivalently in both operation groups (P=0.09 and 0.70). Interestingly, in 80% SBR animals, des-acyl ghrelin peaked on day 1 and acyl ghrelin peaked on day 4 (P=0.0007 and P=0.049 vs controls). GLP-2 secretion was obvious in 80% SBR animals (P=2.25×10−6), which increased immediately and peaked on day 4 (P=0.009 vs. controls). Body weight and food intake in 80% SBR animals recovered to preoperative levels on day 4. Morphological adaptations were evident after day 4. Our results may suggest a management strategy to reinforce these physiological hormone secretion patterns in developing a new therapy for short bowel syndrome.

Mechanical Elongation of the Small Intestine: Evaluation of Techniques for Optimal Screw Placement in a Rodent Model

Introduction. The aim of this study was to evaluate techniques and establish an optimal method for mechanical elongation of small intestine (MESI) using screws in a rodent model in order to develop a potential therapy for short bowel syndrome (SBS). Material and Methods. Adult female Sprague Dawley rats (n = 24) with body weight from 250 to 300 g (Σ = 283) were evaluated using 5 different groups in which the basic denominator for the technique involved the fixation of a blind loop of the intestine on the abdominal wall with the placement of a screw in the lumen secured to the abdominal wall. Results. In all groups with accessible screws, the rodents removed the implants despite the use of washers or suits to prevent removal. Subcutaneous placement of the screw combined with antibiotic treatment and dietary modifications was finally successful. In two animals autologous transplantation of the lengthened intestinal segment was successful. Discussion. While the rodent model may provide useful basic information on mechanical intestinal lengthening, further investigations should be performed in larger animals to make use of the translational nature of MESI in human SBS treatment.