peptide-yy and Short-Bowel-Syndrome

The human small intestine is organized with a proximal-to-distal gradient of mucosal structure and nutrient processing capacity. However, certain nutrients undergo site-specific digestion and absorption, such as iron and folate in the duodenum/jejunum vs vitamin B12 and bile salts in the ileum. Intestinal resection can result in short bowel syndrome (SBS) due to reduction of total and/or site-specific nutrient processing areas. Depending on the segment(s) of intestine resected, malabsorption can be nutrient specific (eg, vitamin B12 or fat) or sweeping, with deficiencies in energy, protein, and various micronutrients. Jejunal resections are generally better tolerated than ileal resections because of greater postresection adaptive capacity than that of the jejunum. Following intestinal resection, energy scavenging and fluid absorption become particularly important in the colon owing to loss of digestive and absorptive surface area in the resection portion. Resection-induced alterations in enteroendocrine cell abundance can further disrupt intestinal function. For example, patients with end jejunostomy have depressed circulating peptide YY and glucagon-like peptide 2 concentrations, which likely contribute to the rapid intestinal transit and blunted intestinal adaptation observed in this population. SBS-associated pathophysiology often extends beyond the gastrointestinal tract, with hepatobiliary disease, metabolic bone disease, D-lactic acidosis, and kidney stone formation being chronic complications. Clinical management of SBS must be individualized to account for the specific nutrient processing deficit within the remnant bowel and to mitigate potential complications, both inside and outside the gastrointestinal tract.

Topics: Adaptation, Physiological; Digestive System Surgical Procedures; Glucagon-Like Peptide 2; Humans; Intestine, Small; Peptide YY; 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

Anecdotal evidence suggests that the colon plays an important role after small bowel resection (SBR). However, colonic changes have not previously been studied. The aim of this study was to characterize morphological and functional changes within the colon after SBR and elucidate the influence of diet complexity on adaptation.. In study 1, 4-week-old piglets underwent a 75% SBR or sham operation and were studied at 2, 4, and 6 weeks postoperation to allow analysis of early and late adaptation responses. Piglets received a polymeric infant formula (PIF). In study 2, SBR piglets received an elemental diet and were studied at 6 weeks postoperation and compared with SBR + PIF piglets from study 1. For both studies, immunohistochemistry was used to quantitate intestinal cell types. Changes in functional proteins were measured by Western blot, enteroendocrine/peptide YY (PYY), enterocyte/liver fatty acid binding protein (L-FABP), and goblet cells/trefoil factor 3 (TFF3).. In study 1, early and late adaptation-related changes were observed after SBR. Early adaptation included increased numbers of enterocytes (P = .0001), whereas late adaptation included increased proliferative cell numbers (P = .02). Enteroendocrine, goblet, and apoptotic cells numbers were significantly elevated in the resected group at all time-points studied (P < .05). Functional changes included increased levels of L-FABP (P = .04) and PYY (P = .03). There was no change in TFF3 expression. In study 2, feeding with an elemental diet resulted in suboptimal adaptation as evidenced by reduced rate of weight gain and significant reductions in total cell numbers (P = .0001), proliferative (P = .0001) and apoptotic cells (P = .04), enteroendocrine cells (P = .001), and PYY expression (P .004).. These findings indicate that significant morphological and functional changes occur in the colon after massive SBR and that these occur as early and late adaptation responses. Elemental diet was associated with suboptimal adaptation suggesting an effect of diet complexity on colonic adaptation.

Topics: Adaptation, Physiological; Animals; Cell Count; Cell Proliferation; Colon; Digestive System Surgical Procedures; Enterocytes; Enteroendocrine Cells; Food, Formulated; Intestine, Small; Models, Animal; Peptide YY; Postoperative Period; Short Bowel Syndrome; Swine

The main reason why enterocyte proliferative effects of peptide YY (PYY) have not been detected in rats undergoing massive small intestinal resection after feeding may have been the background activity of markedly increased endogenous PYY released from L cells in the distal gut in response to the intraluminal nutrients. The purpose of the present study was to evaluate the effects of PYY on enterocyte proliferation in a rat model of distal bowel resection (DBR) with total enteral nutrition (TEN). Male, adult Sprague-Dawley rats were assigned into three experimental groups: sham rats underwent bowel transection and reanastomosis, DBR rats underwent the resection of 40 cm distal small intestine and colon, and DBR-PYY rats underwent distal bowel resection as above, and were treated with PYY(1-36) from day 2 to day 14 postoperatively. During days 2-14 postoperatively, all animals received isocaloric TEN. At the endpoints, plasma PYY levels and parameters of enterocyte proliferation were determined. Compared with the sham group, DBR rats demonstrated a significant decrease in plasma PYY levels, and a significant increase in intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index. Administration of PYY (DBR-PYY group) led to a significant increase in plasma PYY levels, intestinal bowel and mucosal weight, mucosal DNA and protein content, villus height and crypt depth, and crypt cell proliferation index in comparison with the DBR untreated group. We conclude that administration of PYY increases the plasma PYY levels, and PYY induces enterocyte proliferation with TEN after distal bowel resection.

Topics: Animals; Cell Proliferation; Disease Models, Animal; Enteral Nutrition; Enterocytes; Follow-Up Studies; Intestine, Small; Male; Peptide YY; Postoperative Period; Radioimmunoassay; Rats; Rats, Sprague-Dawley; Short Bowel Syndrome; Treatment Outcome

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

Topics: Gastric Emptying; Gastrointestinal Hormones; Humans; Jejunostomy; Peptide YY; Peptides; Short Bowel Syndrome

Short bowel patients with a jejunostomy have large volume stomal outputs, which may in part be due to rapid gastric emptying of liquid. Short bowel patients with a preserved colon do not have such a high stool output and gastric emptying of liquid is normal.. To determine if differences in the gastric emptying rate between short bowel patients with and without a colon can be related to gastrointestinal hormone changes after a meal.. Seven short bowel patients with no remaining colon (jejunal length 30-160 cm) and six with jejunum in continuity with a colon (jejunal length 25-75 cm), and 12 normal subjects.. The subjects all consumed a 640 kcal meal; blood samples were taken for 180 minutes for measurement of gastrointestinal hormones.. Patients with a colon had high fasting peptide YY values (median 71 pmol/l with a colon; 11 pmol/l normal subjects, p < 0.005) with a normal postprandial rise, but those without a colon had a low fasting (median 7 pmol/l, p = 0.076) and a reduced postprandial peptide YY response (p < 0.050). Motilin values were high in some patients without a colon. In both patient groups fasting and postprandial gastrin and cholecystokinin values were high while neurotensin values were low. There were no differences between patient groups and normal subjects in enteroglucagon, pancreatic polypeptide, or somatostatin values.. Low peptide YY values in short bowel patients without a colon may cause rapid gastric emptying of liquid. High values of peptide YY in short bowel patients with a retained colon may slow gastric emptying of liquid and contribute to the "colonic brake'.

Topics: Adult; Aged; Case-Control Studies; Female; Gastric Emptying; Gastrointestinal Hormones; Humans; Jejunostomy; Male; Middle Aged; Peptide YY; Peptides; Short Bowel Syndrome