Intestinal Absorptive Function Research Articles

The application of Ussing chambers for determining the impact of microbes and probiotics on intestinal ion transport

Host-microbe interactions have gained considerable attention in recent years with regards to their role in various organic disorders and diseases. In particular, research efforts have focused on the intestinal microbiota, where the largest and most diverse populations not only co-exist with the host, but also directly influence the state and function of the gastrointestinal (GI) tract. Moreover, both human and animal studies alike are now beginning to show a positive influence of probiotic bacteria on GI disorders associated with diarrhoea or constipation. Diarrheagenic GI diseases, such as those caused by Vibreo cholera or enterpathogenic Eschericia coli, have well-characterised interactions with the host that explain much of the observed symptoms, in particular severe diarrhoea. However, the mechanisms of action of nonpathogenic bacteria or probiotics on host physiology are less clearly understood. In the context of defining the mechanisms of action of probiotics in vitro, the Ussing chamber has proven to be a particularly useful tool. Here, we will present data from several studies that have defined molecular targets for microbes and putative probiotics in the regulation of intestinal secretory and absorptive function, and we will discuss these in the context of their application in pathogen- or inflammation-induced alterations in intestinal ion transport.

Dietary inulin alters the intestinal absorptive and barrier function of piglet intestine after weaning

An experiment was conducted to study the effects of dietary inulin supplementation on the electrophysiological properties of small intestine of suckling and weaned piglets as indicators for glucose absorption and barrier function. Ten sows were divided into two groups, receiving either a control diet, or a diet with 3% inulin. The diets were fed from 3weeks ante partum to 6weeks post partum. In the first 2weeks of life, piglets received only sow’s milk. Irrespective to sex and without castration of males, four piglets (one piglet of each litter) from each group were selected and sacrificed on day 10 of age. The gastrointestinal tract of each piglet was removed and segments were immediately taken from the mid-jejunum and mounted in Ussing chambers. Furthermore, at weaning (6weeks old) 8 piglets were randomly selected irrespective to sex and males were un-castrated (4 animals from sows received control diet and 4 animals from sows received 3% inulin supplemented diet) and fed for 2weeks either control weaning diet or inulin supplemented diet. Thereafter segments of the mid-jejunum were used to investigate the effect of inulin on the gut electrophysiology of weaned piglets. The increase in short-circuit current (Isc) after the addition of glucose is an indicator of higher glucose absorption and the higher tissue conductance (Gt) of the epithelium suggested a higher intestinal permeability to paracellular Na+. In suckling piglets, the addition of d-glucose on the luminal side of the isolated jejunal mucosa increased (P<0.001) the Isc in the inulin-supplemented and control groups compared to basal values. Electrogenic glucose transport (ΔIsc) was similar in suckling piglets from sows fed inulin or control diet, suggesting that feeding of inulin to the mother sows had no effect on glucose absorption across the jejunal mucosa of suckling piglets. However, the dietary inulin supplementation after weaning increased the ΔIsc (P<0.001) compared with the controls, suggesting that the inulin supplementation increased the electrogenic transport of glucose across the jejunal mucosa of weaned piglets indicating higher glucose absorption. Furthermore, the Gt was higher in the inulin-supplemented weaned piglets than in control piglets, which could be due to the increased paracellular permeability to Na+. In conclusion, dietary inulin increased the glucose transport and altered the intestinal barrier by increasing the intestinal permeability in the jejunal mucosa of post-weaned piglets. Furthermore, the results indicated that inulin has a positive effect on glucose absorption in the piglet small intestine after weaning and subsequently the dietary inulin offers a promising approach to avoid post-weaning gastrointestinal tract disorders in pigs.

Dietary supplementation with N-carbamylglutamate increases the expression of intestinal amino acid transporters in weaned Huanjiang mini-pig piglets1

Weaning is associated with reduced intestinal absorptive capacity in piglets. Our previous study indicated that dietary supplementation with N-carbamylglutamate (NCG) enhanced growth performance and improved intestinal function in weaned piglets. The present study was conducted to test the hypothesis that dietary supplementation with NCG may increase the growth performance of weaned piglets by regulating the expression of intestinal nutrient transporters, thus enhancing nutrient absorption. Twenty-four Huanjiang mini-pig piglets weaned at 21 d of age (3.17 ± 0.21 kg average BW) were randomly assigned to 2 dietary treatments consisting of a basal diet and the basal diet with 0.1% NCG supplementation for a 14-d period with 6 pens per treatment and 1 male and 1 female per pen. On d 14, 1 piglet was randomly selected from each pen for blood and tissue sampling. Dietary NCG supplementation enhanced (P < 0.05) growth rate and the efficiency of feed use in weaned Huanjiang mini-pig piglets. The NCG-supplemented diet increased (P < 0.05) mRNA expression levels of Slc6a19, Slc7a9, and Slc1a1 and the protein abundance of ASCT2, B(0)AT1, b(0,+)AT, y(+)LAT1, and EAAC1 in the jejunum. Furthermore, the contents of low density lipoprotein, ammonia, urea nitrogen, and AA as well as the activity of alkaline phosphatase in plasma were all altered (P < 0.05) by supplementation with NCG. These findings indicate that dietary supplementation with NCG may improve intestinal absorptive function in weaned piglets by increasing the expression of AA transporters in the intestine.

Intestinal Absorption and Pancreatic Function are Preserved in Anorexia Nervosa Patients in Both a Severely Malnourished State and After Recovery

Anorexia nervosa (AN) is characterised by a refusal to normal body weight accompanied by a marked restriction of food intake, frequently leading to severe malnutrition. In severe malnutrition and wasting syndromes, mucosal atrophy, altered gastrointestinal motility and pancreatic atrophy, which alter digestive function and can exacerbate malnutrition, have been described. The objective of this work was to determine intestinal absorption and pancreatic function in severely malnourished AN patients before and after recovery. Ten severely malnourished AN women were studied at hospital admittance (body mass index = 11.44-16.16 kg/m(2)) and after weight recovery with artificial nutrition (body mass index ≥ 20 kg/m(2)). A (13)C-labelled triglycerides digestion test, faecal elastase test and d-xylose absorption test were performed. In nine patients, (13)C-labelled triglycerides digestion tests and the faecal elastase and d-xylose tests were normal both before and after weight recovery. In one patient, the results were abnormal, and they led to the detection of a previously undiagnosed celiac disease in addition to her AN. In this series, there was neither intestinal absorption nor pancreatic function disturbances in severely malnourished AN patients either before or after weight recovery. The usefulness of these tests in the differentiation of functional versus structural changes needs further studies.

Morphological Adaptation in Adult Short Bowel Syndrome Undergoing Intestinal Rehabilitation

ABSTRACTObjectives: To observe the adaptive changes of the intestinal mucosa in patients with short bowel syndrome (SBS) who received intestinal rehabilitation therapy and further evaluate the feasibility of the magnifying endoscopy for monitoring intestinal adaptation. Method: Ten patients with SBS received growth hormone (GH) (0.05 mg/kg/day), oral glutamine (30 g/day), plus enteral nutrition (EN) for 4 weeks. Intestinal absorptive function, mucosal morphology, proliferating, and apoptotic status were investigated before and after treatment. Result: All patients completed the treatment. Intestinal absorptive function and villus height were significantly improved after treatment (p < .05). Furthermore, the proliferation levels of the small bowel were increased (p < .05). In addition, we also found that magnifying endoscopy can well describe the microscopic changes of intestinal mucosa. Conclusion: Treatment with GH, glutamine, and EN has positive effect on intestinal mucosal morphologic adaptation in patients with SBS. Furthermore, magnifying endoscopy for monitoring intestinal adaptation is practicable and reliable.

The Human Fecal Microbiota Metabolizes Deoxynivalenol and Deoxynivalenol-3-Glucoside and May Be Responsible for Urinary Deepoxy-Deoxynivalenol

Deoxynivalenol (DON) is a potent mycotoxin produced by Fusarium molds and affects intestinal nutrient absorption and barrier function in experimental and farm animals. Free DON and the plant metabolite DON-3-β-d-glucoside (D3G) are frequently found in wheat and maize. D3G is stable in the upper human gut, but some human intestinal bacteria release DON from D3G in vitro. Furthermore, some bacteria derived from animal digestive systems degrade DON to a less toxic metabolite, deepoxy-deoxynivalenol (DOM-1). The metabolism of D3G and DON by the human microbiota has not been fully assessed. We therefore conducted in vitro batch culture experiments assessing the activity of the human fecal microbiota to release DON from D3G. We also studied detoxification of DON to DOM-1 by the microbiota and its potential effect on urinary DON excretion in humans. Fecal slurry from five volunteers was spiked with DON or D3G and incubated anaerobically (from 1 h to 7 days), and mycotoxins were extracted into acetonitrile. Mycotoxins were detected in fecal extracts and urine by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The fecal microbiota released DON from D3G very efficiently, with hydrolysis peaking after 4 to 6 h. The fecal microbiota from one volunteer transformed DON to DOM-1. Urine from the same volunteer also contained DOM-1 (4.7% of DON), whereas DOM-1 was not detectable in urine from other volunteers. Our results confirm that the fecal microbiota releases DON from its glycosylated form, hence increasing the toxic burden in exposed individuals. Furthermore, this is first evidence that the human fecal microbiota of one volunteer detoxifies DON, resulting in the appearance of DOM-1 in urine.

The impoverished gut—a triple burden of diarrhoea, stunting and chronic disease

More than one-fifth of the world's population live in extreme poverty, where a lack of safe water and adequate sanitation enables high rates of enteric infections and diarrhoea to continue unabated. Although oral rehydration therapy has greatly reduced diarrhoea-associated mortality, enteric infections still persist, disrupting intestinal absorptive and barrier functions and resulting in up to 43% of stunted growth, affecting one-fifth of children worldwide and one-third of children in developing countries. Diarrhoea in children from impoverished areas during their first 2 years might cause, on average, an 8 cm growth shortfall and 10 IQ point decrement by the time they are 7-9 years old. A child's height at their second birthday is therefore the best predictor of cognitive development or 'human capital'. To this 'double burden' of diarrhoea and malnutrition, data now suggest that children with stunted growth and repeated gut infections are also at increased risk of developing obesity and its associated comorbidities, resulting in a 'triple burden' of the impoverished gut. Here, we Review the growing evidence for this triple burden and potential mechanisms and interventions that must be understood and applied to prevent the loss of human potential and unaffordable societal costs caused by these vicious cycles of poverty.

Comparison of Lifor and UW Solution for Cryopreservation of Canine Small Intestinal Grafts

Background and objective: Organ preservation is one of three key techniques in transplantation, which is also the backbone of organ transplant. Ideal preservation solution is always one of the hot spot of organ transplant because it can provide suitably physiological and biochemical microenvironment and prolong the organ storage time. UW solution is regarded as the gold standard for organ preservation solution because of its better outcome in clinical transplantation. However, its high viscosity and could cause red blood cell aggregation - both negatively affecting wash-out and reperfusion. In order to prevent a transient increase in serum potassium concentration and cause cardiac arrest, the potassium-rich UW solution need to be flushed out from the organ prior to reperfusion. In addition, the price of UW solution is expensive. Therefore, above shortcomings make it not fully satisfied with the clinical demands and limit its widespread application. Lifor solution is a new kind of organ preservation solution, which is based on the merits of current various organ preservation solutions. The aim of current study was to investigate the cryopreservation of Lifor organ preservation solution in preserving canine small intestine. Methods: A total of 24 canines were randomly divided into two groups: Lifor group and UW group. Canine in each group were preserved for 6 and 9 hours respectively. The preservation effect of Lifor solution was compared with UW solution in the swine segmental small bowel autotransplantation model. After cold preservation, histological changes and the content of ATP in the small intestinal mucosa were analyzed. Then intestinal absorptive function was studied. Results: After 6h and 9h cold preservation, pathological changes, the content of ATP in the intestinal mucosa and intestinal absorptive function in Lifor group had no significant difference from those of UW group. Conclusion: The effect of 6h and 9h cryopreservation of canine small bowel with Lifor solution is similar to those of UW solution.

Metabolomic markers for intestinal ischemia in a mouse model

BackgroundDiagnosis of intestinal ischemia remains a clinical challenge. The aim of the present study was to use a metabolomic protocol to identify upregulated and downregulated small molecules (Mr < 500) in the serum of mice with intestinal ischemia. Such molecules could have clinical utility when evaluated as biomarkers in human studies. MethodsA mouse model for intestinal ischemia was established and validated using histology and serum tumor necrosis factor α concentrations. A second mouse model of peritoneal sepsis was used as a positive control. Serial serum samples were collected from these and from sham-operated animals. Sera were analyzed by gas chromatography–mass spectrometry for 40 small molecules as their trimethylsilyl and O-methyloxime derivatives. Peak areas were normalized against an internal standard and resultant peak area ratios subjected to multivariate data analysis using unsupervised principal components analysis and supervised orthogonal projection to latent structures–discriminant analysis. Upregulated and downregulated serum molecules were identified from their correlation to the orthogonal projection to latent structures–discriminant analysis model. ResultsThree highly significantly upregulated (fold-change) serum molecules in intestinal ischemia were inorganic phosphate (2.4), urea (4.3), and threonic acid (2.9). Five highly significantly downregulated (fold-change) serum molecules were stearic acid (1.7), arabinose (2.7), xylose (1.6), glucose (1.4), and ribose (2.2). Lactic acid remained unchanged in intestinal ischemia. ConclusionsDistinct molecular changes are reported here for the first time in intestinal ischemia. They reveal impairments of gut microbiota metabolism, intestinal absorption, and renal function, together with increased oxidative stress. In contrast to other reports, lactic acid was not significantly changed. These molecular signatures may now be evaluated in clinical studies.

Controlling Salmonella infection in weanling pigs through water delivery of direct-fed microbials or organic acids: Part II. Effects on intestinal histology and active nutrient transport1

The objective of this study was to evaluate the effects of water-delivered, direct-fed microbials (DFM) or organic acids on intestinal morphology and active nutrient absorption in weanling pigs after deliberate Salmonella infection. Pigs (n = 88) were weaned at 19 ± 2 d of age and assigned to 1 of the following treatments, which were administered for 14 d: 1) control diet; 2) control diet + DFM (Enterococcus faecium, Bacillus subtilis, and Bacillus licheniformis) in drinking water at 10(9) cfu/L for each strain of bacteria; 3) control diet + organic acid-based blend (predominantly propionic, acetic, and benzoic acids) in drinking water at 2.58 mL/L; and 4) control diet + 55 mg/kg carbadox. Pigs were challenged with 10(10) cfu Salmonella enterica var Typhimurium 6 d after commencement of treatments. Pigs (n = 22/d) were harvested before Salmonella challenge and on d 2, 4, and 8 after challenge. Duodenal, jejunal, and ileal mucosal tissues were sampled for measurement of villus height and crypt depth. Jejunal tissue was sampled for determination of active nutrient absorption in modified Ussing chambers. Duodenal villus height was greater in pigs fed in-feed antibiotic before infection (P < 0.05). Jejunal crypts were deeper in DFM- and acid-treated pigs on d 4 after infection compared with all other treatments (P < 0.05). Salmonella infection resulted in a linear decrease in phosphorus (P < 0.001) and glucose (P < 0.05) active transport, and an increase (P < 0.001) in glutamine uptake immediately after challenge. Salmonella infection reduced basal short-circuit current (I(sc)); however, water-delivered DFM or organic acid treatments caused greater basal I(sc) on d 2 after challenge than did carbadox. Carbachol-induced chloride ion secretion was greatest in negative control pigs before infection (P < 0.01) and DFM-treated pigs (P < 0.05) after infection. In conclusion, both the DFM and acidification treatments induced increases in basal active ion movement and jejunal crypt depth, which could be interpreted as responses consistent with increased Salmonella pathology, but none of the additives markedly affected intestinal absorptive and secretory function in response to Salmonella challenge.

Delayed enteral feeding impairs intestinal carbohydrate absorption in critically ill patients*

Delay in initiating enteral nutrition has been reported to disrupt intestinal mucosal integrity in animals and to prolong the duration of mechanical ventilation in humans. However, its impact on intestinal absorptive function in critically ill patients is unknown. The aim of this study was to examine the impact of delayed enteral nutrition on small intestinal absorption of 3-O-methyl-glucose. Prospective, randomized study. Tertiary critical care unit. Studies were performed in 28 critically ill patients. Patients were randomized to either enteral nutrition within 24 hrs of admission (14 "early feeding": 8 males, 6 females, age 54.9 ± 3.3 yrs) or no enteral nutrition during the first 4 days of admission (14 "delayed feeding": 10 males, 4 females, age 56.1 ± 4.2 yrs). Gastric emptying (scintigraphy, 100 mL of Ensure (Abbott Australia, Kurnell, Australia) with 20 MBq Tc-suphur colloid), intestinal absorption of glucose (3 g of 3-O-methyl-glucose), and clinical outcomes were assessed 4 days after intensive care unit admission. Although there was no difference in gastric emptying, plasma 3-O-methyl-glucose concentrations were less in the patients with delayed feeding compared to those who were fed earlier (peak: 0.24 ± 0.04 mmol/L vs. 0.37 ± 0.04 mmol/L, p < .02) and integrated (area under the curve at 240 mins: 38.5 ± 7.0 mmol/min/L vs. 63.4 ± 8.3 mmol/min/L, p < .04). There was an inverse correlation between integrated plasma concentrations of 3-O-methyl-glucose (area under the curve at 240 mins) and the duration of ventilation (r = -.51; p = .006). In the delayed feeding group, both the duration of mechanical ventilation (13.7 ± 1.9 days vs. 9.2 ± 0.9 days; p = .049) and length of stay in the intensive care unit (15.9 ± 1.9 days vs. 11.3 ± 0.8 days; p = .048) were greater. In critical illness, delaying enteral feeding is associated with a reduction in small intestinal glucose absorption, consistent with the reduction in mucosal integrity after nutrient deprivation evident in animal models. The duration of both mechanical ventilation and length of stay in the intensive care unit are prolonged. These observations support recommendations for "early" enteral nutrition in critically ill patients.

Side-to-side isoperistaltic strictureplasty for chronic ischemic enteritis: report of a case

Chronic ischemic enteritis can cause intestinal strictures, but extensive resection of the small intestine may leave patients with short bowel syndrome. Thus, the importance of preserving diseased small bowel is now recognized. We report a case of successful side-to-side isoperistaltic strictureplasty (SSIS), performed to prevent short bowel syndrome, in a patient with ischemic enteritis caused by strangulated intestinal obstruction. SSIS is useful for preserving the intestinal absorptive function in patients with a long narrowed bowel loop caused by ischemic change. To our knowledge, this is the first report of the successful treatment of a long stricture resulting from ischemic enteritis, achieved by performing SSIS.

Bone Marrow Stromal Cell Transplantation Mitigates Radiation-Induced Gastrointestinal Syndrome in Mice

BackgroundNuclear accidents and terrorism presents a serious threat for mass casualty. While bone-marrow transplantation might mitigate hematopoietic syndrome, currently there are no approved medical countermeasures to alleviate radiation-induced gastrointestinal syndrome (RIGS), resulting from direct cytocidal effects on intestinal stem cells (ISC) and crypt stromal cells. We examined whether bone marrow-derived adherent stromal cell transplantation (BMSCT) could restitute irradiated intestinal stem cells niche and mitigate radiation-induced gastrointestinal syndrome.Methodology/Principal FindingsAutologous bone marrow was cultured in mesenchymal basal medium and adherent cells were harvested for transplantation to C57Bl6 mice, 24 and 72 hours after lethal whole body irradiation (10.4 Gy) or abdominal irradiation (16–20 Gy) in a single fraction. Mesenchymal, endothelial and myeloid population were characterized by flow cytometry. Intestinal crypt regeneration and absorptive function was assessed by histopathology and xylose absorption assay, respectively. In contrast to 100% mortality in irradiated controls, BMSCT mitigated RIGS and rescued mice from radiation lethality after 18 Gy of abdominal irradiation or 10.4 Gy whole body irradiation with 100% survival (p<0.0007 and p<0.0009 respectively) beyond 25 days. Transplantation of enriched myeloid and non-myeloid fractions failed to improve survival. BMASCT induced ISC regeneration, restitution of the ISC niche and xylose absorption. Serum levels of intestinal radioprotective factors, such as, R-Spondin1, KGF, PDGF and FGF2, and anti-inflammatory cytokines were elevated, while inflammatory cytokines were down regulated.Conclusion/SignificanceMitigation of lethal intestinal injury, following high doses of irradiation, can be achieved by intravenous transplantation of marrow-derived stromal cells, including mesenchymal, endothelial and macrophage cell population. BMASCT increases blood levels of intestinal growth factors and induces regeneration of the irradiated host ISC niche, thus providing a platform to discover potential radiation mitigators and protectors for acute radiation syndromes and chemo-radiation therapy of abdominal malignancies.

Magnesium-deficiency does not alter calcineurin inhibitors activity in mice

Introduction Tacrolimus (TAC) and cyclosporin (CsA) are commonly responsible for hypomagnesemia that predisposes in turn for hypertension, renal impairment and encephalopathy. Objective The effects of TAC on Mg 2+-homeostasis and of pre-existing Mg 2+-deficiency on TAC immunosuppressive activity were compared to CsA in mice. Methods Mg 2+ was quantified in plasma, erythrocytes, urine, feces, and femurs from mice treated with TAC 5 mg/kg/day. Immunosuppression was assessed in splenocytes by mixed lymphocyte reaction, IL-2 quantification and CN activity determination. Results Plasma and urine Mg 2+ levels in TAC-treated mice were significantly lower from day 7 until day 21 (p < 0.05 versus control) and returned to control value at day 28. Mg 2+ levels were unchanged in erythrocyte, feces and femur. Inhibition of allogeneic proliferation, IL-2 production and CN activity were 68, 56 and 30% lower (p < 0.01) after 7 days of TAC-treatment, and 72, 68 and 51% lower (p < 0.01) after 7 days of CsA-treatment with a dose of 50 mg/kg/day. Dietary-induced hypomagnesemia resulted in significant inhibition of CN activity (p < 0.01) without alteration of IL-2 production or allogeneic proliferation. However, it did not alter the effects observed with CsA- or TAC-treatment on allogeneic proliferation, IL-2 production and CN activity. Conclusion By contrast with CsA, long-course TAC-treatment induced an early, but transient, and moderate hypomagnesemia without alteration of bone or erythrocyte stocks, intestinal absorption or renal function. Therefore, in clinical use, TAC should be preferred to CsA in patients with pathological or pharmacological conditions which favor Mg 2+-deficiency. However, dietary-induced hypomagnesemia did not alter the immunosuppressive effects of TAC and CsA.

Effects of an early lipopolysaccharide challenge on growth and small intestinal structure and function of broiler chickens

Hu, X. F., Guo, Y. M., Li, J. H., Yan, G. L., Bun, S. and Huang, B. Y. 2011. Effects of an early lipopolysaccharide challenge on growth and small intestinal structure and function of broiler chickens. Can. J. Anim. Sci. 91: 379–384. Two experiments were conducted to determine the effect of early exposure to lipopolysaccharide (LPS) on small intestinal structure and function of broiler chickens. Seven-day-old birds were randomly allotted to two equal treatments: an LPS-injected treatment in which the birds were injected intraperitoneally with LPS 500 µg kg−1 body weight (dissolved in 1 mL saline) on 8, 10, 12, 15, 17, and 19 d of age, i.e., on days 1, 3, and 5 d for 2 continuous weeks, and a control treatment (CTRL) in which the birds were similarly injected with 1 mL saline as a placebo. In exp. 1, food intake and weight gain were monitored over the 2 wk, the weight of the small bowel was determined at 14 and 21 d of age and duodenal and jejunal villus height and crypt depth, D-xylose uptake were also measured at 21 d. In exp. 2, additional measurements of the intestinal peristalsis ratio and the BrdU-labeling index and duodenal sodium-glucose co-transporter-1 (SGLT1) mRNA level were made at 21 d of age. The results showed that LPS challenge decreased feed intake, daily gain, duodenal and jejunal villus height and crypt depth, plasma D-xylose concentration and intestinal BrdUrd-labeling index, respectively (P&lt;0.05) as well as small bowel weight at 14 and 21 d of age (P&lt;0.05). Conversely, LPS injection increased SGLT1 mRNA level in the small intestine (P&lt;0.05) and the small intestinal relative weight at 14 (P&lt;0.05) and 21 d of age (P=0.063). Following LPS injection there were non-significant changes in feed conversion ratio and intestinal peristalsis ratio (P&gt;0.05). In conclusion, early LPS challenge delayed the growth of intestine and impaired small intestinal structure and absorptive function.

Management of acute intestinal failure

Intestinal failure (IF) occurs when intestinal absorptive function is inadequate to maintain hydration and nutrition without enteral or parenteral supplements. It has been classified into three types depending on duration of nutrition support and reversibility. Type 1 IF is commonly seen in the peri-operative period as ileus and usually spontaneously resolves within 14 d. Type 2 IF is uncommon and is often associated with an intra-abdominal catastrophe, intestinal resection, sepsis, metabolic disturbances and undernutrition. Type 3 IF is a chronic condition in a metabolically stable patient, which usually requires long-term parenteral nutrition. This paper focuses on Types 1 and 2 IF (or acute IF) that are usually found in surgical wards. The objectives of this paper are to review the incidence, aetiology, prevention, management principles and outcome of acute IF. The paper discusses the resources necessary to manage acute IF, the indications for inter-hospital transfer and the practicalities of how to transfer and receive a patient with acute IF.

Growth Hormone for Intestinal Adaptation in Patients With Short Bowel Syndrome: Systematic Review and Meta-Analysis of Randomized Controlled Trials

Objectives The purpose of this systematic review was to assess the efficacy of growth hormone (GH) treatment in patients with short bowel syndrome (SBS). Methods Electronic searches were performed to identify all publications describing randomized controlled trials (RCTs) on the use of GH with or without glutamine for the treatment of patients with SBS. The outcomes of interest were body weight, lean body mass, and intestinal absorption function. Results Four trials involving 70 patients were included in the review. A meta-analysis of these trials suggested that GH had a positive effect in terms of increased weight (mean difference [MD] = 1.66; 95% CI, 0.69–2.63, P < 0.001), lean body mass (MD = 1.93; 95% CI, 0.97–2.90; P < 0.001), energy absorption (MD = 4.42; 95% CI, 0.26–8.58; P = 0.04), nitrogen absorption (MD = 4.85; 95% CI, 0.20–9.49; P = 0.04), and fat absorption (MD = 5.02; 95% CI, 0.21–9.82; P = 0.04) for patients with SBS. Adverse effects occurred during active treatment in all trials. Only 1 trial included a 12-week follow-up study. Conclusions The results suggest a possible short-term benefit in terms of body weight, lean body mass, and absorptive capacities; however, no conclusion of long-term efficacy of GH could be obtained. Large-scale, long-term follow-up RCTs are needed to confirm the efficacy and tolerability of GH in the future.

Studies on bacterial endotoxin and intestinal absorption function in patients with chronic heart failure

BackgroundSmall intestinal function may be altered in decompensated chronic heart failure (CHF) and translocating LPS may contribute to systemic inflammation observed in CHF. MethodsWe measured intestinal permeability (melibiose and rhamnose), active (3-O-methyl-d-glucose (3-OMG)) and passive (d-xylose) carrier-mediated absorption in 20 CHF patients (12 edematous and 8 non-edematous) and 8 controls by saccharide absorption technique assessing urinary recovery of orally administered sugars. We additionally measured LPS concentrations in 42 patients with decompensated heart failure and after recompensation. ResultsCHF patients had a 54% reduction of active carrier-mediated intestinal transport compared to controls (p<0.0001). This reduction was strongest in edematous compared to non-edematous patients and controls (recovery in urine: 13.2±2.0% vs. 20.8±2.4% vs. 36.0±3.7%, all p≤0.05). Patients showed a 34% reduction of passive carrier-mediated transport, strongest in edematous patients (p=0.006). A greater impairment of active carrier-mediated transport remained significant after adjustment for non-mucosal factors in CHF (p=0.0004). Non carrier-mediated intestinal permeability was not altered. Data from 42 decompensated patients showed a decrease in LPS after recompensation (p=0.004).Edematous patients had highest blood concentrations of LPS, TNF and sTNF-R1 (p<0.04). CHF patients with abnormal LPS concentrations >0.50EU/mL (n=7) had the highest concentrations of TNF (7.0±1.6 vs. 3.1±0.3pg/mL, p<0.02), and sTNF-R1 (3499±52 vs. 1599±219 pg/mL, p=0.02). ConclusionActive carrier-mediated intestinal transport is reduced in decompensated CHF indicating epithelial dysfunction possibly as a consequence of intestinal ischemia. Higher LPS concentrations in edematous CHF relate to inflammation. LPS decreased after recompensation. This suggests a cause/effect relationship between edematous gut wall, epithelial dysfunction and translocating LPS.

The relationship between intestinal histology and function as shown by compensatory enlargement of remnant villi after midgut resection in chickens

To demonstrate the relationship between intestinal histology and function, we investigated the possibility that compensatory enlargement of villi in the chickens' remnant intestine can be induced after 50% or 80% jejunal resection as well as after 50% jejunal plus 70% ileal resection. Compared with intact control chickens, operated chickens showed an almost similar body weight, nitrogen retention, and ether extract digestibility, an improved dry matter digestibility, and a much greater absorption of protein and ether extract by the remnant jejunum and ileum. This suggests an enhanced absorptive function of the remnant intestine. In these chickens, increased value of most light microscopic parameters, increased frequency of anastomosing of each villus, and increased number of protuberated epithelial cells appeared with an increase in the intestinal resection area. This suggests that intestinal villi and epithelial cells are hypertrophied in the remnant jejunum and ileum, and that intestinal villi adapt to activated intestinal absorptive function not by increasing their numbers, but by fusing together into larger villi. These findings demonstrate that intestinal histology is intimately related to intestinal function.

Alterations in the proteome of the NHERF1 knockout mouse jejunal brush border membrane vesicles

Na/H exchanger regulatory factor 1 (NHERF1) is a scaffold protein made up of two PDZ domains and an ERM binding domain. It is in the brush border of multiple epithelial cells where it modulates 1) Na absorption by regulating NHE3 complexes and cytoskeletal association, 2) Cl secretion through trafficking of CFTR, and 3) Na-coupled phosphate absorption through membrane retention of NaPi2a. To further understand the role of NHERF1 in regulation of small intestinal Na absorptive cell function, with emphasis on apical membrane transport regulation, quantitative proteomic analysis was performed on brush border membrane vesicles (BBMV) prepared from wild-type (WT) and homozygous NHERF1 knockout mouse jejunal villus Na absorptive cells. Jejunal architecture appeared normal in NHERF1 null; however, there was increased proliferative activity, as indicated by increased crypt BrdU staining. LC-MS/MS analysis using iTRAQ to compare WT and NHERF1 null BBMV identified 463 proteins present in both WT and NHERF1 null BBMV of simultaneously prepared and studied samples. Seventeen proteins had an altered amount of expression between WT and NHERF1 null in two or more separate preparations, and 149 total proteins were altered in at least one BBMV preparation. The classes of the majority of proteins altered included transport proteins, signaling and trafficking proteins, and proteins involved in proliferation and cell division. Affected proteins also included tight junction and adherens junction proteins, cytoskeletal proteins, as well as metabolic and BB digestive enzymes. Changes in abundance of several proteins were confirmed by immunoblotting [increased CEACAM1, decreased ezrin (p-ezrin), NHERF3, PLCβ3, E-cadherin, p120, β-catenin]. The changes in the jejunal BBMV proteome of NHERF1 null mice are consistent with a more complex role of NHERF1 than just forming signaling complexes and anchoring proteins to the apical membrane and include at least alterations in proteins involved in transport, signaling, and proliferation.