The ability to provide parenteral support represents a revolutionary change in medical therapy for patients with temporary and inadequate intestinal absorptive capacity or for patients with chronic ...intestinal failure due to digestive diseases. Nevertheless, due to the rarity of intestinal failure, a de facto policy of “discrimination by organ failure treatment” exists in many countries whereby this problem is under-recognized and under-treated. With the increasing recognition of the pathophysiological consequences of intestinal resection and the occurrence of new pro-adaptive treatments for patients suffering from short bowel syndrome, this review reflects on the history of developments in this area and discusses current practice and future directions of the field.
Short bowel syndrome (SBS) is a rare gastrointestinal condition that is defined as having less than 200 cm of remaining small intestine. SBS results from extensive surgical resection and is ...associated with a high risk for intestinal failure (IF) with a need for parenteral support (PS). Depending on the region of intestinal resection, three different main anatomy types can be distinguished from each other. In this review, we synthesize the current knowledge on the role of the colon in the setting of SBS-IF with a colon-in-continuity (SBS-IF-CiC), e.g., by enhancing the degree of intestinal adaptation, energy salvage, and the role of the microbiota. In addition, the effect of the disease-modifying treatment with glucagon-like peptide-2 (GLP-2) analogs in SBS-IF-CiC and how it differs from patients without a colon will be discussed. Overall, the findings explained in this review highlight the importance of preservation of the colon in SBS-IF.
Scope
Biomarkers for intake of green leafy vegetables such as spinach can help investigate their health effects. However, only few potential intake markers have been reported in the literature so ...far.
Methods and Results
Based on a cross‐over study on whole leaf and minced spinach, we investigate changes in metabolites before and after spinach intake and differences between the two treatments and health status. Nineteen volunteers (12 healthy subjects and 7 short bowel patients) completed the study within 48 days. Urine samples (24‐h intervals before and after spinach intake) and serum samples (baseline, post 8 d, and post 15 d) are collected and analyzed by ultra‐high performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UHPLC‐QTOF‐MS). The acquired data is analyzed by multivariate and univariate analyses. Three candidate biomarkers are observed in urine only after the spinach intake, including des‐amino arginine pentenol ester, D/L‐malic acid ester of cis‐p‐coumarate, D/L‐malic acid ester of trans‐p‐coumarate, and 69 metabolites are present before spinach intake but showing an altered level after treatment. These metabolites are related to dietary habits or meal structure, and some changes are possibly affected by spinach intake. The candidate biomarkers are independent of spinach pre‐processing and healthy status. No markers are discovered in serum samples.
Conclusion
We propose structures for three candidate spinach intake biomarkers; these markers will need further validation in independent studies.
Three biomarkers of spinach intake (BFIs) and 69 “effect‐like” biomarkers were found after untargeted profiling of urine before and after spinach comsumption. The BFIs are independent of 1) spinach pre‐processing and 2) presence of a large intestine. The 69 “effect‐like” biomarkers were found to be related to volunteers’ dietary habits (wholegrain rye, coffee) or to provided foods during the study.
Accumulating evidence implicates glucagon-like peptide-1 (GLP-1) to have, beyond glucose maintenance, a beneficial role in the gastrointestinal tract. Here, we review emerging data investigating ...GLP-1 as a novel treatment for intestinal diseases, including inflammatory bowel diseases, short-bowel syndrome, intestinal toxicities and coeliac disease. Possible beneficial mechanisms for these diseases include GLP-1's influence on gastric emptying, its anti-inflammatory properties and its intestinotrophic effect. The current knowledge basis derives from the available GLP-1 agonist treatments in experimental animals and small clinical trials. However, new novel strategies including dual GLP-1/GLP-2 agonists are also in development for the treatment of intestinal diseases.
Efficient lipid digestion in formula-fed infants is required to ensure the availability of fatty acids for normal organ development. Previous studies suggest that the efficiency of lipid digestion ...may depend on whether lipids are emulsified with soy lecithin or fractions derived from bovine milk. This study, therefore, aimed to determine whether emulsification with bovine milk-derived emulsifiers or soy lecithin (SL) influenced lipid digestion in vitro and in vivo. Lipid digestibility was determined in vitro in oil-in-water emulsions using four different milk-derived emulsifiers or SL, and the ultrastructural appearance of the emulsions was assessed using electron microscopy. Subsequently, selected emulsions were added to a base diet and fed to preterm neonatal piglets. Initially, preterm pigs equipped with an ileostomy were fed experimental formulas for seven days and stoma output was collected quantitatively. Next, lipid absorption kinetics was studied in preterm pigs given pure emulsions. Finally, complete formulas with different emulsions were fed for four days, and the post-bolus plasma triglyceride level was determined. Milk-derived emulsifiers (containing protein and phospholipids from milk fat globule membranes and extracellular vesicles) showed increased effects on fat digestion compared to SL in an in vitro digestion model. Further, milk-derived emulsifiers significantly increased the digestion of triglyceride in the preterm piglet model compared with SL. Ultra-structural images indicated a more regular and smooth surface of fat droplets emulsified with milk-derived emulsifiers relative to SL. We conclude that, relative to SL, milk-derived emulsifiers lead to a different surface ultrastructure on the lipid droplets, and increase lipid digestion.
Exogenous Glucagon-Like Peptide-2 (GLP-2) treatment improves intestinal wet weight absorption in short bowel syndrome (SBS) patients. In healthy subjects, administration of GLP-2 increases small ...intestinal blood flow. The aim of the study was to evaluate the effect of GLP-2 on mesenteric blood flow and dynamic changes in cardiac parameters in SBS patients with jejunostomy and varying length of remnant small intestine.
8 SBS patients with end-jejunostomy and less than 200
cm small intestine were given GLP-2, 1600
μg subcutaneously (SC), or isotonic saline in a double blinded manner. At 0, 30 and 60
min plasma GLP-2 was measured, and from 0 to 90
min, blood flow in the superior mesenteric artery (SMA) and the celiac artery (CA) was measured using Doppler ultrasound (US), and cardiovascular variables were measured by continuous impedance cardiography and finger plethysmography.
Plasma GLP-2 concentrations increased significantly in the GLP-2 group, whereas no changes were seen in the placebo group. Compared to baseline, GLP-2 SC elicited a 19.4% decrease (p
<
0.01) in the resistance index (RI) and a 97.6% increase in time averaged maximal velocity (TAMV) in the SMA (P
<
0.01). In the CA there were no significant changes in RI or TAMV in the GLP-2 or placebo group. Blood flow and length of remaining intestine were correlated (RI: y
=
0.14
+
4.3, R
=
0.83, p
=
0.01 and TAMV: y
=
1.21
+
21.3, R
=
0.63, p
=
0.09).
GLP-2 non significantly increased cardiac output (CO), stroke volume (SV) and significantly increased heart rate (HR) compared to baseline.
Subcutaneous GLP-2 increased SMA blood flow in end-jejunostomy SBS patients with less than 200
cm of remaining small intestine. The increase in blood flow correlated with the length of remaining intestine, suggesting that the increase is coupled to the metabolic actions of GLP-2 on the gut rather than effects on the vasculature.
► Exogenous GLP-2 administration increases mesenteric blood flow in SBS patients. ► Increase in blood flow seems to correlate to the length of remaining small intestine. ► The findings suggest that the increase is coupled to the metabolic actions of GLP-2.
Introduction
Parenteral nutrition-associated cholestasis (PNAC) is a complication of long-term parenteral nutrition (PN). Removal of lipids may reverse PNAC but compromises the energy to ensure ...infant growth. The purpose of this study was to test whether a low-fat, high-carbohydrate PN regimen, which prevents and reverses PNAC in adults, could do the same in infants. This regimen could potentially avoid the problem of diminished energy input after removing nutritional lipids.
Methods
Infants developing PNAC over a 2-year period were started on a low-fat PN regimen with calories primarily from carbohydrates. The fat-free PN, containing 314 kJ/ml, was provided 5–6 times a week and fat, including essential fatty acids and fat-soluble vitamins, 1–2 times a week. Enteral feeding was continued according to individual tolerance.
Results
The study included 10 infants with short bowel syndrome (six with intestinal failure due to necrotizing enterocolitis, one with gastroschisis, one with complications due to unrecognized anal atresia and two with midgut volvulus). Median duration of PN with fat before initiating the low-fat regime was 69 days (25–75 % percentile: 41–75 days), and mean s-bilirubin was 139 µmol/l (range 87–323 µmol/l). Median duration with low-fat regimen was 69 days (25–75 % percentile: 18–123 days). Bilirubin reversed to normal (<50 µmol/l) in all infants. Seven children showed catch-up growth. No essential fatty acid deficiency, steatosis or deaths were observed.
Conclusions
A low-fat, high-carbohydrate PN regimen together with enteral feeding is well tolerated and may be used in reversing liver disease in PN-dependent infants without compromising growth.
Abstract Objective The prevalence of obesity and related co-morbidities is reaching pandemic proportions. Today, the most effective obesity treatments are glucagon-like peptide 1 (GLP-1) analogs and ...bariatric surgery. Interestingly, both intervention paradigms have been associated with adaptive growth responses in the gut; however, intestinotrophic mechanisms associated with or secondary to medical or surgical obesity therapies are poorly understood. Therefore, the objective of this study was to assess the local basal endogenous and pharmacological intestinotrophic effects of glucagon-like peptides and bariatric surgery in mice. Methods We used in situ hybridization to provide a detailed and comparative anatomical map of the local distribution of GLP-1 receptor ( Glp1r ), GLP-2 receptor ( Glp2r ), and preproglucagon ( Gcg ) mRNA expression throughout the mouse gastrointestinal tract. Gut development in GLP-1R-, GLP-2R-, or GCG-deficient mice was compared to their corresponding wild-type controls, and intestinotrophic effects of GLP-1 and GLP-2 analogs were assessed in wild-type mice. Lastly, gut volume was determined in a mouse model of vertical sleeve gastrectomy (VSG). Results Comparison of Glp1r , Glp2r , and Gcg mRNA expression indicated a widespread, but distinct, distribution of these three transcripts throughout all compartments of the mouse gastrointestinal tract. While mice null for Glp1r or Gcg showed normal intestinal morphology, Glp2r−/− mice exhibited a slight reduction in small intestinal mucosa volume. Pharmacological treatment with GLP-1 and GLP-2 analogs significantly increased gut volume. In contrast, VSG surgery had no effect on intestinal morphology. Conclusion The present study indicates that the endogenous preproglucagon system, exemplified by the entire Gcg gene and the receptors for GLP-1 and GLP-2, does not play a major role in normal gut development in the mouse. Furthermore, elevation in local intestinal and circulating levels of GLP-1 and GLP-2 achieved after VSG has limited impact on intestinal morphometry. Hence, although exogenous treatment with GLP-1 and GLP-2 analogs enhances gut growth, the contributions of endogenously-secreted GLP-1 and GLP-2 to gut growth may be more modest and highly context-dependent.
ObjectivePatients with short bowel syndrome (SBS) and colon in continuity have better adaptation potential compared with patients with jejunostomy. Adaptation may involve enhanced postprandial ...secretion of the enteroendocrine hormones glucagon-like peptide (GLP)-1 and GLP-2 which are normally degraded by dipeptidyl peptidase (DPP)-4. Nevertheless, some patients with SBS with colon in continuity suffer from high-volume faecal excretions and have been shown to benefit from treatment with GLP-2. Therefore, we aimed to evaluate efficacy of sitagliptin, a DPP-4 inhibitor, on reducing faecal excretions in this patient group.DesignIn an open-label, case series, proof-of-concept pilot study, 100 mg oral sitagliptin was given two times per day for 8 weeks to patients with SBS with ≥50% colon in continuity with or without the need for parenteral support (PS). To assess intestinal function, metabolic balance studies were done at baseline and following 8 weeks of treatment.ResultsOf the 10 patients planned for enrolment, 8 patients were included; 7 patients completed the study. Although postprandial endogenous GLP-2 concentrations increased by 49 hours×pmol/L (39, 105; p=0.018) (median (min, max)), sitagliptin did not significantly reduce median faecal wet weight (−174 g/day (−1510, 675; p=0.176)) or increase intestinal wet weight absorption. However, heterogeneity in the treatment effect was observed: intestinal wet weight absorption increased in all four patients with intestinal failure. One patient achieved a reduction in PS by 500 mL per administration day.ConclusionFollowing this negative, small pilot study, larger, placebo-controlled, studies are needed to establish the therapeutic potential of DPP-4 inhibition in patients with SBS.
Short bowel syndrome results from surgical resection, congenital defect or disease-associated loss of absorption. Parenteral support (PS) is lifesaving in patients with short bowel syndrome and ...intestinal failure who are unable to compensate for their malabsorption by metabolic or pharmacologic adaptation. Together, the symptoms of short bowel syndrome and the inconvenience and complications in relation to PS (e.g. catheter-related blood steam infections, central thrombosis and intestinal failure associated liver disease) may impair the quality of life of patients. The aim of treatment is to maximize intestinal absorption, minimize the inconvenience of diarrhea, and avoid, reduce or eliminate the need for PS to achieve the best possible quality of life for the patient. Conventional treatments include dietary manipulations, oral rehydration solutions, and antidiarrheal and antisecretory treatments. However, the evidence base for these interventions is limited and treatments that improve the structural and functional integrity of the remaining intestine are needed. Teduglutide, an analog of glucagon-like peptide 2, improves intestinal rehabilitation by promoting mucosal growth and possibly by restoring gastric emptying and secretion, thereby reducing intestinal losses and promoting intestinal absorption. In a 3-week, phase II balance study, teduglutide reduced diarrhea by around 700 g/day and fecal energy losses by around 0.8 MJ/day. In two randomized, placebo-controlled, 24-week, phase III studies, similar findings were obtained when evaluating the fluid composite effect, which is the sum of the beneficial effects of teduglutide – reduction in the need for PS, increase in urine production and reduction in oral fluid intake. The fluid composite effect reflects the increase in intestinal fluid absorption (and the concomitant reduction in diarrhea) and may be used in studies in which metabolic balance assessments are not performed. In studies of up to 24 weeks’ duration, teduglutide appears to be safe and well tolerated. Treatment with teduglutide was associated with enhancement or restoration of the structural and functional integrity of the remaining intestine with significant intestinotrophic and proabsorptive effects, facilitating a reduction in diarrhea and an equivalent reduction in the need for PS in patients with short bowel syndrome and intestinal failure.
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