glucagon-like-peptide-1 and Short-Bowel-Syndrome

Short bowel syndrome (SBS) is the most common cause of chronic intestinal failure, requiring home parenteral support (intravenous fluid, parenteral nutrition, or parenteral nutrition with intravenous fluid) to compensate for severe malabsorption. The loss of mucosal absorptive area after extensive intestinal resection is accompanied by an accelerated transit and hypersecretion. Changes in physiology and clinical outcomes differ between patients with SBS with or without the distal ileum and/or colon-in-continuity. This narrative review summarizes the treatments used in SBS, with a focus on novel approaches with intestinotrophic agents. During the early postoperative years, spontaneous adaptation occurs and can be induced or accelerated with conventional therapies, which include dietary and fluid modifications and antidiarrheal and antisecretory drugs. Based on the proadaptive role of enterohormones (eg, glucagon-like peptide [GLP]-2), analogues have been developed to allow enhanced or hyperadaptation after a period of stabilization. Teduglutide is the first GLP-2 analogue developed and commercialized with proadaptive effects resulting in reduced parenteral support needs; however, the potential for weaning of parenteral support is variable. Whether early treatment with enterohormones or accelerated hyperadaptation would further improve absorption and outcomes remains to be shown. Longer-acting GLP-2 analogues are currently being investigated. Encouraging reports with GLP-1 agonists require confirmation in randomized trials, and dual GLP-1 and GLP-2 analogues have yet to be clinically investigated. Future studies will prove whether the timing and/or combinations of different enterohormones will be able to break the ceiling of intestinal rehabilitation in SBS.

Topics: Gastrointestinal Agents; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestines; 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.

Topics: Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestine, Small; Quality of Life; Short Bowel Syndrome

The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies. The discovery that GLP-2 promotes mucosal growth in the intestine is described, and key findings from both preclinical studies and the GLP-2 clinical development program for short bowel syndrome (SBS) are reviewed. Finally, we summarize recent progress in GLP biology, highlighting emerging concepts and scientific insights with translational relevance.

Topics: Animals; Diabetes Mellitus, Type 2; Drug Discovery; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor; Humans; Short Bowel Syndrome; Structure-Activity Relationship

The approval of teduglutide, a recombinant analog of human glucagon-like peptide (GLP) 2, by the US Food and Drug Administration (Gattex) and the European Medicines Agency (Revestive) has illustrated the potential of selected gut hormones as treatments in patients with short-bowel syndrome and intestinal failure. Gut hormones may improve the structural and functional intestinal adaptation following intestinal resection by decreasing a rapid gastric emptying and hypersecretion, by increasing the intestinal blood flow, and by promoting intestinal growth. This review summarizes the findings from phase 2 and 3 teduglutide studies, and pilot studies employing GLP-1 and agonists for this orphan condition.. In a 3-week, phase 2, metabolic balance study, teduglutide increased the intestinal wet weight absorption by approximately 700 g/day and reduced fecal energy losses by approximately 0.8 MJ/day (∼200 Kcal/day). In two subsequent 24-week, phase 3 studies, teduglutide reduced the need for parenteral support in the same magnitude. Adverse events were mainly of gastrointestinal origin and consistent with the known mechanism of action of teduglutide. Pilot studies suggest that GLP-1 may be less potent. Synergistic effects may be seen by co-treatment with GLP-2.. Gut hormones promote intestinal adaptation and absorption, decreasing fecal losses, thereby decreasing or even eliminating the need for parenteral support. This will aid the intestinal rehabilitation in these severely disabled short-bowel syndrome patients.

Topics: Clinical Trials, Phase II as Topic; Gastrointestinal Agents; Glucagon-Like Peptide 1; Humans; Intestinal Absorption; Intestine, Small; Parenteral Nutrition; Peptides; Pilot Projects; Quality of Life; Short Bowel Syndrome; United States

Glucagon and the glucagon-like peptides (GLPs) are derived from single proglucagon gene and exhibit an increasing number of biologically important actions. As a counter-regulatory hormone for insulin, glucagon plays a critical role in maintaining glucose homeostasis in vivo in both animals and humans. To increase blood glucose, glucagon promotes hepatic glucose output by increasing glycogenolysis and gluconeogenesis and by decreasing glycogenesis and glycolysis in a concerted fashion via multiple mechanisms. The glucagon-like peptides GLP-1 and GLP-2 are produced in enteroendocrine L cells of the small and large intestine and secreted in a nutrient-dependent manner. GLP-1 regulates nutrient assimilation via inhibition of gastric emptying and food intake. GLP-1 controls blood glucose following nutrient absorption via stimulation of glucose-dependent insulin secretion, insulin biosynthesis, islet proliferation, and neogenesis and inhibition of glucagon secretion. Glucagon-like peptide-1 (GLP-1 is an insulinotropic hormone, GLP-1 also inhibits glucagon secretion. GLP-1 lowers blood glucose in normal subjects and in patients with type 2 diabetes. The major biological action of GLP-2 appears to be the stimulation of small-bowel hyperplasia, manifested by an increases in both villous height and small-bowel weight. A pilot study of GLP-2 administration in human subjects with short bowel syndrome demonstrated significant improvements in energy absorption, bone density, increased body weight, which correlated with increased crypt plus villus height on intestinal biopsy sections. The biological actions of two of these glucagon-related peptides, suggest that they may have therapeutic relevance for the treatment of human diseases such as diabetes, selective intestinal disorders and cardiac diseases.

Topics: Animals; Blood Glucose; Gastrointestinal Hormones; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestinal Diseases; Intestinal Mucosa; Islets of Langerhans; Peptide Fragments; Peptides; Pilot Projects; Protein Precursors; Short Bowel Syndrome; Signal Transduction

Glucagon-like peptide 2 (GLP-2) is a member of family of peptides derived from the proglucagon gene expressed in the intestines, pancreas and brain. Tissue-specific posttranslational processing of proglucagon leads to GLP-2 and GLP-1 secretion from the intestine and glucagon secretion from the pancreas. GLP-2 and GLP-1 are co-secreted from the enteroendocrine L-cells located in distal intestine in response to enteral nutrient ingestion, especially carbohydrate and fat. GLP-2 secretion is mediated by direct nutrient stimulation of the L-cells and indirect action from enteroendocrine and neural inputs, including GIP, gastrin-releasing peptide (GRP) and the vagus nerve. GLP-2 is secreted as a 33-amino acid peptide and is rapidly cleaved by dipeptidylpeptidase IV (DPP-IV) to a truncated peptide which acts as a weak agonist with competitive antagonistic properties. GLP-2 acts to enhance nutrient absorption by inhibiting gastric motility and secretion and stimulating nutrient transport. GLP-2 also suppresses food intake when infused centrally. The trophic actions of GLP-2 are specific for the intestine and occur via stimulation of crypt cell proliferation and suppression of apoptosis in mucosal epithelial cells. GLP-2 reduces gut permeability, bacterial translocation and proinflammatory cytokine expression under conditions of intestinal inflammation and injury. The effects of GLP-2 are mediated by a G-protein-linked receptor that is localized to the intestinal mucosa and hypothalamus. The intestinal localization of the GLP-2R to neural and endocrine cells, but not enterocytes, suggests that its actions are mediated indirectly via a secondary signaling mechanism. The implications of GLP-2 in domestic animal production are largely unexplored. However, GLP-2 may have therapeutic application in treatment of gastrointestinal injury and diarrheal diseases that occur in developing neonatal and weanling animals.

Topics: Amino Acid Sequence; Animals; Animals, Domestic; Cattle; Chickens; Dogs; Gene Expression; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-1 Receptor; Humans; Molecular Sequence Data; Peptides; Receptors, Glucagon; Rodentia; Sequence Homology; Short Bowel Syndrome; Swine

The glucagon-like peptides GLP-1 and GLP-2 are synthesised and then released from enteroendocrine cells in the small and large intestine. GLP-1 promotes efficient nutrient assimilation while GLP-2 regulates energy absorption via effects on nutrient intake, gastric acid secretion and gastric emptying, nutrient absorption, and mucosal permeability. Preliminary human studies indicate that GLP-2 may enhance energy absorption and reduce fluid loss in subjects with short bowel syndrome suggesting that GLP-2 functions as a key regulator of mucosal integrity, permeability, and nutrient absorption. Hence GLP-2 may be therapeutically useful in diseases characterised by injury or dysfunction of the gastrointestinal epithelium.

Topics: Adaptation, Physiological; Animals; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestinal Diseases; Intestines; Mice; Peptide Fragments; Peptides; Protein Precursors; Rats; Short Bowel Syndrome

The ileocolonic brake is impaired in short bowel syndrome (SBS) patients with distal bowel resections. An attenuated meal-stimulated hormone secretion may cause gastric hypersecretion, rapid gastric and intestinal transit and a poor adaptation. Attempting to restore this ileocolonic brake, this study evaluated the acute effects of continuous intravenous administration of glucagon-like peptide (GLP) 1 and 2, alone or in combination, on gastrointestinal function in SBS patients.. SBS patients were admitted 4 times for identical 72-h balance studies, where infusions (1 pmol/kg/min) of GLP-1, placebo (saline), GLP-2 and GLP-1+2 (1 pmol/kg/min of each), were provided. Patients filled out a VAS questionnaire regarding subjective symptoms during treatments. Bone mineral content, body-weight and -composition were measured using DEXA scans. Blood glucose, insulin, pro insulin C-peptide and GLP concentrations were measured in relation to a standardized breakfast.. Nine SBS patients (5 women/4 men, aged 52±11) were enrolled and completed the study; 7 had end-jejunostomies, 2 had 50% of colon-in-continuity. All treatments significantly reduced the fecal wet weight, energy, nitrogen, sodium and potassium losses compared to placebo. However, only GLP-2 containing treatments increased absolute absorption of wet weight and sodium. Only GLP-1+2 improved the hydrational status evaluated by DEXA increases in the fat mass and calculated total body weight. GLP-1 and GLP-1+2 reduced the post-prandial blood glucose levels. A tendency of nausea and reduced appetite was seen in relation to GLP-1 treatment, but this was ameliorated by the co-administration of GLP-2.. GLP-1 decreased diarrhea and fecal excretions in SBS patients, but it seems less potent than GLP-2. The combination of GLP-1+2 numerically provided additive effects on intestinal absorption compared to either peptide given alone. Larger, long-term studies should further assess the potential of the glucagon-like peptides or analogs, alone or in combination, in the treatment of SBS patients.

Topics: Blood Glucose; C-Peptide; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Intestinal Absorption; Male; Middle Aged; Placebos; Short Bowel Syndrome

Extensive intestinal resection may lead to short bowel (SB) syndrome, resulting in intestinal insufficiency or intestinal failure (IF). Intestinal insufficiency and IF involve deficiency of the proglucagon-derived hormones glucagon-like peptide-1 (GLP-1) and GLP-2. Two major problems of SB are epithelial surface loss and accelerated transit. Standard treatment now targets intestinal adaptation with a GLP-2 analogue to enlarge absorptive surface area. It is possible that additional benefit can be gained from a combination of GLP-1 and GLP-2 activity, with the aim to enlarge intestinal surface area and slow intestinal transit.. The GLP-1- and GLP-2-specific effects of the novel dual GLP-1 receptor (GLP-1R) and GLP-2 receptor (GLP-2R) agonist dapiglutide (rINN) were characterized in rodents. Furthermore, in a murine SB model of intestinal insufficiency with 40% ileocecal resection, the influence of dapiglutide on intestinal growth, body weight, food intake, volume status, and stool water content was tested against vehicle and sham-operated male mice.. Dapiglutide significantly improves oral glucose tolerance, reduces intestinal transit time, and promotes intestinal growth. In the SB mouse model, dapiglutide promotes body weight recovery, despite unchanged intake of liquid diet. Dapiglutide promotes significant intestinal growth, as indicated by significantly increased villus height as well as intestinal length. Furthermore, dapiglutide reduces stool water losses, resulting in reduced plasma aldosterone.. Dapiglutide possesses specific and potent GLP-1R and GLP-2R agonist effects in rodents. In the murine SB model, combined unimolecular GLP-1R and GLP-2R stimulation with dapiglutide potently attenuates intestinal insufficiency and potentially also IF.

Topics: Animals; Body Weight; Disease Models, Animal; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-2 Receptor; Male; Mice; Short Bowel Syndrome; Water

Short bowel syndrome can occur after extensive intestinal resection, causing intestinal insufficiency or intestinal failure, which requires long-term parenteral nutrition. Glucagon-like peptide-2 (GLP-2) pharmacotherapy is now clinically used to reduce the disease burden of intestinal failure. However, many patients still cannot be weaned off from parenteral nutrition completely. The novel dual GLP-1 and GLP-2 receptor agonist dapiglutide has previously been shown to be highly effective in a preclinical murine short bowel model. Here, we studied the effects of dapiglutide on intestinal epithelial barrier function. In the jejunum, dapiglutide increased claudin-7 expression and tightened the paracellular tight junction leak pathway. At the same time, dapiglutide promoted paracellular tight junction cation size selectivity in the jejunum. This was paralleled by extension of the cation selective tight junction proteins claudin-2 and claudin-10b and preserved claudin-15 expression and localization along the crypt-villus axis in the jejunum. In the colon, no barrier effects from dapiglutide were observed. In the colon, dapiglutide attenuated the short bowel-associated, compensatorily increased epithelial sodium channel activity, likely secondary, by improved volume status. Future studies are needed to address the intestinal adaptation of the colon.

Topics: Animals; Claudins; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Glucagon-Like Peptide-2 Receptor; Humans; Intestinal Mucosa; Mice; Short Bowel Syndrome

The 2021 Gairdner Prize is awarded to Daniel Drucker, Joel Habener, and Jens Juul Holst for the discovery of novel peptides encoded in the proglucagon sequence and the establishment of their physiological roles. These discoveries underpinned the development of therapeutics that are now benefiting patients with type 2 diabetes and other disorders worldwide.

Topics: Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Islets of Langerhans; Proglucagon; Receptors, Glucagon; Short Bowel Syndrome

Energy deprivation leads to a decrease in white adipose tissue and bone mineral density (BMD), while simultaneously inducing the expansion of marrow adipose tissue (MAT). In short bowel syndrome (SBS), parenteral nutrition mitigates the deterioration of nutritional status, including decreases in MAT. Osteoporosis is, however, a frequent complication of SBS. The objective of our study here was to evaluate the association of fat deposit sites (subcutaneous and visceral adipose tissues: intrahepatic lipid (IHL) and MAT) and the incretin glucagon-like peptide 1 (GLP1) with BMD in individuals with SBS. MAT was negatively correlated with lumbar spine BMD in normal individuals, but not in those in the SBS group, who otherwise showed a positive correlation between MAT and GLP1. In addition, in individuals with SBS, IHL was negatively associated with lumbar spine BMD and positively associated with C-terminal telopeptide of type 1 collagen (a serum biomarker of bone turnover). Caloric maintenance in individuals with SBS, therefore, seems to positively affect the relationship between MAT and BMD, which may be modulated, at least in part, by GLP1.

Topics: Adipose Tissue; Adult; Bone Density; Bone Marrow; Bone Remodeling; Case-Control Studies; Cross-Sectional Studies; Female; Glucagon-Like Peptide 1; Humans; Incretins; Male; Middle Aged; Osteoporosis; Parenteral Nutrition; Short Bowel Syndrome

Short bowel syndrome (SBS) patients developing hyperphagia have a better outcome. Gastrointestinal endocrine adaptations help to improve intestinal functions and food behaviour. We investigated neuroendocrine adaptations in SBS patients and rat models with jejuno-ileal (IR-JI) or jejuno-colonic (IR-JC) anastomosis with and without parenteral nutrition. Circulating levels of ghrelin, PYY, GLP-1, and GLP-2 were determined in SBS rat models and patients. Levels of mRNA for proglucagon, PYY and for hypothalamic neuropeptides were quantified by qRT-PCR in SBS rat models. Histology and immunostaining for Ki67, GLP-1 and PYY were performed in SBS rats. IR-JC rats, but not IR-JI, exhibited significantly higher crypt depths and number of Ki67-positive cells than sham. Fasting and/or postprandial plasma ghrelin and PYY concentrations were higher, or tend to be higher, in IR-JC rats and SBS-JC patients than in controls. Proglucagon and Pyy mRNA levels were significantly enhanced in IR-JC rats. Levels of mRNA coding hypothalamic orexigenic NPY and AgRP peptides were significantly higher in IR-JC than in sham rats. We demonstrate an increase of plasma ghrelin concentrations, major changes in hypothalamic neuropeptides levels and greater induction of PYY in SBS-JC rats and patients suggesting that jejuno-colonic continuity creates a peculiar environment promoting further gut-brain adaptations.

Topics: Adult; Aged; Agouti-Related Protein; Anastomosis, Surgical; Animals; Colon; Disease Models, Animal; Feeding Behavior; Female; Ghrelin; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Hyperphagia; Hypothalamus; Intestinal Mucosa; Jejunum; Ki-67 Antigen; Male; Middle Aged; Neuropeptide Y; Peptide YY; Proglucagon; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; RNA, Messenger; Short Bowel Syndrome

Short bowel syndrome (SBS) is a serious clinical disorder characterized by diarrhea and nutritional deprivation. Glucagon-like peptide-1 (GLP-1) is a key hormone, produced by L-cells in the ileum, that regulates proximal gut transit. When extensive ileal resection occurs, as in SBS, GLP-1 levels may be deficient. In this study, we test whether the use of GLP-1 agonist exenatide can improve the nutritional state and intestinal symptoms of patients with SBS.. Five consecutive patients with SBS based on ≤90 cm of small bowel and clinical evidence of nutritional deprivation were selected. Baseline SBS symptoms, demographic and laboratory data were obtained. Antroduodenal manometry was performed on each subject. Each patient was then started on exenatide and over the following month, the baseline parameters were repeated.. The subjects consisted of four males and one female, aged 46-69 years. At baseline, all had severe diarrhea that ranged from 6 to 15 bowel movements per day, often occurring within minutes of eating. After exenatide, all five patients had immediate improvement in bowel frequency and form; bowel movements were no longer meal-related. Total parenteral nutrition was stopped successfully in three patients. Antroduodenal manometry revealed continuous low amplitude gastric contractions during fasting which completely normalized with exenatide.. Exenatide is a novel and safe treatment option for SBS. It produced substantial improvement in the bowel habits, nutritional status and quality of life of SBS patients. Successful treatment with exenatide may significantly reduce the need for parenteral nutrition and small bowel transplant.

Topics: Aged; Exenatide; Female; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Male; Manometry; Middle Aged; Nutritional Status; Parenteral Nutrition, Total; Peptides; Retrospective Studies; Short Bowel Syndrome; Venoms

The glucagon-like peptides (GLP) 1 and 2 are secreted postprandially from L cells located mainly in the ileum. Both hormones prolong intestinal transit and GLP-2 is intestinotrophic in rodents. Patients with a jejunostomy have poor adaptation, rapid gastric and intestinal transit, and impaired postprandial GLP-2 secretion. Ileum resected short bowel patients with a preserved colon show evidence of functional adaptation and have normal gastric emptying.. To investigate if GLP-1 and GLP-2 contribute to the positive effects of a preserved colon in short bowel patients by measuring circulating levels of GLP-1 and GLP-2 in seven ileum resected short bowel patients with a preserved colon and seven age and sex matched controls.. GLP-1 and GLP-2 immunoreactivity was measured by specific radioimmunoassays in plasma collected at fasting and at regular intervals 180 minutes after a test meal.. Median (25-75%) fasting GLP-2 values were 72 (69-105) pmol/l versus 23 (19-27) pmol/l (p=0.001) and meal stimulated area under the curve was 21 078 (14 811-26 610) min x pmol/l versus 11 150 (7151-12 801) min x pmol/l (p=0.01) in short bowel patients with a preserved colon compared with control subjects. Fasting GLP-1 values were 10 (6-12) pmol/l versus 5 (3-5) pmol/l (p=0.01) and meal stimulated area under the curve was 3418 (2966-6850) min x pmol/l versus 2478 (1929-3199) min x pmol/l (p=0.04), respectively.. Ileum resected short bowel patients with a preserved colon had elevated fasting plasma concentrations of GLP-1 and GLP-2 and significantly larger meal stimulated areas under the curve compared with age and sex matched controls. Elevated GLP-1 and GLP-2 concentrations may contribute to the positive effects of a preserved colon on intestinal motility and functional adaptation in ileum resected short bowel patients.

Topics: Adaptation, Physiological; Adult; Aged; Area Under Curve; Case-Control Studies; Fasting; Female; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Humans; Ileum; Male; Middle Aged; Peptide Fragments; Peptides; Postprandial Period; Protein Precursors; Radioimmunoassay; Short Bowel Syndrome

The small intestine's large capacity for glucose absorption and for adaptation seems to contradict the reported importance of carbohydrate malabsorption in short bowel (SB) patients. The aim of the present study was to investigate the occurrence of malabsorption in these patients ingesting realistic amounts of carbohydrates. We performed a dose-response study [ingestion of increasing amounts of glucose and complex carbohydrates (boiled rice and wheat bread), and the nonabsorbable disaccharide lactulose] in SB patients with an intact colon. The hydrogen (H2) -breath test and changes in serum acetate were used to evaluate colonic fermentation and, thus, indirectly, the lack of small intestinal carbohydrate assimilation. Blood glucose and plasma insulin were measured to evaluate absorption. Plasma concentrations of the ileal brake hormones--glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY)--were measured to test whether release of these hormones was related to colonic fermentation. Significant amounts of 25 g and 50 g glucose, and of the bread and rice meals were fermented rather than absorbed, as judged by the increases in end-expiratory H2. Serum acetate concentrations were significantly higher in SB patients than in healthy controls. The orocecal transit times of all test meals ranged from 15 to 120 min. GLP-1 and PYY releases in SB patients were significantly higher than in healthy volunteers. They were mutually parallel and paralleled the increase in insulin. They were not related to ongoing fermentation or to intraluminal carbohydrate content per se, but most probably to absorption of glucose in the distal bowel. In conclusion, well-adapted SB patients had pronounced small intestinal malabsorption of carbohydrate, even after ingestion of small amounts of easily absorbable carbohydrates. A fast small intestinal spreading of carbohydrates, once in the small intestine, and a spill-over to the colon seem to explain the data best.

Topics: Adult; Aged; Bacteria; Carbohydrate Metabolism; Colon; Digestion; Female; Fermentation; Glucagon; Glucagon-Like Peptide 1; Humans; Intestinal Absorption; Intestine, Small; Middle Aged; Peptide Fragments; Peptide YY; Protein Precursors; Short Bowel Syndrome