Background and aims: Glucagon-like peptide 2 (GLP-2) may improve intestinal absorption in short bowel syndrome (SBS) patients with an end jejunostomy. Teduglutide (ALX-0600), a dipeptidyl peptidase IV resistant GLP-2 analogue, prolongs the intestinotrophic properties of GLP-2 in animal models. The safety and effect of teduglutide were investigated in SBS patients with and without a colon in continuity. Methods: Teduglutide was given subcutaneously for 21 days once or twice daily to 16 SBS patients in the per protocol investigational group, 10 with end jejunostomy (doses of 0.03 (n = 2), 0.10 (n = 5), or 0.15 (n = 3) mg/kg/day), one with ,50% colon in continuity (dose 0.03 mg/kg/day), and five with >50% colon in continuity (dose 0.10 mg/kg/day). Nutrient balance studies, D-xylose tests, and intestinal mucosa biopsies were performed at baseline, on the last three days of treatment, and after three weeks of follow up. Pre-study fasting native GLP-2 levels were determined for the five patients with >50% colon in continuity.Results: Pooled across groups and compared with baseline, teduglutide increased absolute (+743 (477) g/day; p,0.001) and relative (+22 (16)%; p,0.001) wet weight absorption, urine weight (+555 (485) g/day; p,0.001), and urine sodium excretion (+53 (40) mmol/day; p,0.001). Teduglutide decreased faecal wet weight (2711 (734) g/day; p = 0.001) and faecal energy excretion (2808 (1453) kJ/day (2193 (347) kcal/day); p = 0.040). In SBS patients with end jejunostomy, teduglutide significantly increased villus height (+38 (45)%; p = 0.030), crypt depth (+22 (18)%; p = 0.010), and mitotic index (+115 (108)%; p = 0.010). Crypt depth and mitotic index did not change in colonic biopsies from SBS patients with colon in continuity. The most common side effects were enlargement of the stoma nipple and mild lower leg oedema. The improvements in intestinal absorption and decreases in faecal excretion noted after treatment had reversed after the drug free follow up period. A controlled study with a more robust design is ongoing in order to determine the optimal dosage of teduglutide for SBS patients to achieve the maximal effect and utility of this drug in clinical practice. Conclusion: Teduglutide, at three dose levels for 21 days, was safe and well tolerated, intestinotrophic, and significantly increased intestinal wet weight absorption in SBS patients with an end jejunostomy or a colon in continuity.

Background & Aims: Glucagon-like peptide 2 (GLP-2) is intestinotrophic, antisecretory, and transit-modulating in rodents, and it is mainly secreted from the intestinal mucosa of the terminal ileum and colon after food ingestion. We assessed the effect of GLP-2 on the gastrointestinal function in patients without a terminal ileum and colon who have functional short-bowel syndrome with severe malabsorption of wet weight (>1.5 kg/day) and energy (>2.3 MJ/day) and no postprandial secretion of GLP-2. Methods: Balance studies were performed before and after treatment with GLP-2, 400 g subcutaneously twice a day for 35 days, in 8 patients (4 -17 years from last bowel resection; 6 with Crohn's disease). Four patients received home parenteral nutrition (mean residual jejunum, 83 cm), and 4 did not (mean ileum resection, 106 cm). Biopsy specimens were taken from jejunal/ileal stomas, transit was measured by scintigraphy, and body composition was measured by dual-energy x-ray absorptiometry. Results: Treatment with GLP-2 improved the intestinal absorption of energy 3.5% ؎ 4.0% (mean ؎ SD) from 49.9% to 53.4% (P ‫؍‬ 0.04), wet weight 11% ؎ 12% from 25% to 36% (P ‫؍‬ 0.04), and nitrogen 4.7% ؎ 5.4% from 47.4% to 52.1% (P ‫؍‬ 0.04). Body weight increased 1.2 ؎ 1.0 kg (P ‫؍‬ 0.01), lean body mass increased 2.9 ؎ 1.9 kg (P ‫؍‬ 0.004), fat mass decreased 1.8 ؎ 1.3 kg (P ‫؍‬ 0.007), and 24-hour urine creatinine excretion increased (P ‫؍‬ 0.02). The time to 50% gastric emptying of solids increased 30 ؎ 16 minutes from 89 to 119 minutes (P < 0.05). Small bowel transit time was not changed. Crypt depth and villus height were increased in 5 and 6 patients, respectively. Conclusions: Treatment with GLP-2 improves intestinal absorption and nutritional status in short-bowel patients with impaired postprandial GLP-2 secretion in whom the terminal ileum and the colon have been resected.

Five European laboratories tested a simple in vitro batch system for dietary fibre fermentation studies, The inoculum was composed of fresh human faeces mixed with a carbonatephosphate buffer complex supplemented with trace elements and urea. Five dietary fibre sources (cellulose, sugarbeet fibre, soyabean fibre, maize bran and pectin) were used by each laboratory on three occasions to determine pH, residual non-starch polysaccharides (NSP) and short-chain fatty acid production during fermentation. Cellulose and maize bran degradabilities were very low (7.2 (SE 10.8) and 6 2 (SE 9.1) % respectively after 24h), whereas pectin and soyabean fibre were highly degraded (97.4 (~~4 . 4 ) and 91.1 ( s~3 . 4 ) % respectively after 24 h). Sugarbeet fibre exhibited an intermediate level of degradability (595 (SE 149) %). Short-chain fatty acid production was closely related to NSP degradation (r 0.99). Although each variable was ranked similarly by all laboratories, some differences occurred with respect to absolute values. However, the adaptation of donors to the experimental substrates was not an influential factor. Interlaboratory differences could be reduced either by adding less substrate during incubations or using less-diluted inocula. In vitro fermentations with inocula made from human faeces and from rat caecal contents gave similar results. There was a close correspondence between the data obtained in the present experiment and those previously published in in vivo studies in the rat using the same fibres. The in v i m batch system tested during the present study provides a rapid means of obtaining quantitative estimates of the fermentation and the estimation of the energy content of new sources of dietary fibre.

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Background-Glucagon-like peptide 2 (GLP-2) is a growth factor for the intestinal epithelium in rodents and may aVect intestinal transit. Aims-To study the GLP-2 response to nutrient ingestion in seven short bowel patients with intestinal failure and seven controls. Methods-The patients and controls were admitted twice for two test meals after a night of fasting. Meal A was liquid (300 ml, 1.88 MJ); meal B was a regular breakfast (755 g, 3.92 MJ). Plasma samples were collected for 180 minutes; GLP-2 immunoreactivity was measured with an NH 2 terminal specific radioimmunoassay. Results-Both meals elicited significant increases in plasma GLP-2 in controls. The magnitude and duration of the responses were dependent on the meal size: the maximum median (25-75%) increases after meal A and B were 24 (3-28) and 48 (33-56) pmol/l. Plasma GLP-2 returned to basal concentrations 180 minutes after meal A, but remained at 50% of peak values after meal B. In the patients neither meal significantly changed the GLP-2 concentration; the maximum median elevation after meal B was 5 (2-8) pmol/l. There were significant diVerences between patients and controls with respect to the GLP-2 responses to meals A and B. Conclusion-Identification of GLP-2 as a tissue specific intestinal growth factor and demonstration of an impaired meal stimulated GLP-2 response in short bowel patients raises the possibility that GLP-2 administration may constitute a new therapeutic strategy, enhancing jejunal adaptation in ileum resected short bowel patients with intestinal failure.

Short chain fatty acids (SCFAs) (Gut 1995; 37: 684-689)

Background-Medium chain C8-C10 triglycerides (MCTs) improve fat absorption in short bowel patients. EVects on overall energy absorption remain unknown. Aims-To determine whether MCTs and medium chain fatty acids (MCFAs) are absorbed in the colon like the short chain fatty acids (SCFAs) or are lost in faeces similarly to long chain fatty acids (LCFAs). Methods-Nine small bowel resected patients without and 10 with a colon in continuity excreted 2-6 MJ/day and were randomised and crossed over between two high fat diets (10 MJ/day, 50% as fat), based on either long chain triglycerides (LCT) alone or equal quantities of LCT and MCT. Results-Patients with a colon absorbed C8-C10 fatty acids considerably better than patients without a colon at similar and extreme levels of LCFA malabsorption; the colonic impact on absorption of C14-18 fatty acids was negligible. MCT redoubled fat (MCT+LCT) absorption from 23% to 58% in patients with a colon, and increased overall bomb calorimetric energy absorption from 46% to 58%. The increase in fat absorption from 37% to 46% in patients without a colon did not improve overall energy absorption because malabsorption of carbohydrate and protein increased. Conclusion-In small bowel resected patients, the colon seems to serve as a digestive organ for medium chain fat, probably absorbed as MCFAs, perhaps because like the SCFAs, they are water soluble. Only patients with a colon gained from MCT treatment. (Gut 1998;43:478-483) Keywords: absorption; medium chain fatty acid; colon; short bowel Carbohydrate and protein that escape absorption in the small bowel are metabolised by the colonic bacteria to short chain fatty acids (SCFAs), which are readily absorbed in the large bowel. This type of digestion is well known from the rumen and large bowels of plant eating animals, and it represents a means of salvaging energy in patients with short bowel and preserved colonic function, having been shown to reduce faecal energy excretion by 2-4 MJ/day. [1][2][3] Medium chain triglyceride (MCT) has been applied in therapy when assimilation of dietary long chain triglyceride (LCT) is diminished. A reduction in steatorrhoea has been taken as the clinical argument for this treatment, and emphasis has been placed on the more rapid absorption of MCT in the small bowel.4 5 The human colon is not usually considered as a site of fat absorption, although studies have indicated that colonic absorption of the medium chain fatty acids (MCFAs) C8:0 and C10:0 takes place in dog 6 and rat. 7 8 The increase in octanoic acid in peripheral blood after rectal installation in patients with cirrhosis, 9 and the rectal absorption of octanoic acid from dialysis bags 10 implies that MCFAs are absorbed in the human rectum.The awareness of SCFA absorption in the large bowel prompted us to investigate whether the favourable absorption also holds for MCFAs, and to what extent preserved colonic function exerted an influence on the eYcacy of MCT treatment in patients with small bowel resection. Material and methods PAT...