The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.

To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.

Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.

The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.

The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.

Delayed gastric emptying (DGE) represents a significant cause for morbidity following pancreatoduodenectomy (PD). At a time when no specific and universally effective therapy exists to treat these patients, elucidating other potential (preventable or treatable) mechanisms for DGE is important. The aim of the manuscript was to test the hypothesis that ileal brake contributes to DGE in PD patients receiving jejunal tube feeding by systematically reviewing experimental and clinical literature. A series of clinically relevant questions were framed related to the potential role of the ileal brake in development of DGE post-PD and formed the basis of targeted literature searches. A comprehensive search of major reference databases from January 1980 to June 2015 was carried out which included human and animal studies. The ileal brake is a feedback loop neurally mediated by the vagus and sympatho-adrenergic pathways and hormonally by gut peptides including glucagon-like peptide-1, peptide YY (PYY), and neurotensin. The most potent stimulus for this inhibitory reflex is intra-ileal fat. There is evidence to indicate the role of an inhibitory reflex (on gastric emptying) mediated by PYY and CCK which, in turn, are stimulated by nutrient delivery into the distal small intestine providing indirect support to the role of ileal brake in post-PD DGE. The ileal brake is a likely factor contributing to DGE post-PD. While there has been no study to directly test this hypothesis, there is compelling indirect evidence to support it. Designing a trial that would answer such a question appears to be the most appropriate way forward.

Peptide YY (PYY) is affected in several gastrointestinal diseases and disorders. Changes in PYY appear to be an adaptive response to alterations in pathophysiological conditions caused by the disease. This applies to gastrointestinal diseases/disorders such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, systemic sclerosis, and post-intestinal resection. By contrast, the changes in PYY in chronic idiopathic slow transit constipation (CST) seem to be of a primary nature, and may be one etiological factor of the disease. Abnormalities in PYY seem to contribute to the development of symptoms present in irritable bowel syndrome, inflammatory bowel disease, gastroenteropathy in long-standing diabetes and CST. The changes in PYY could, however, be favorable in some gastrointestinal disorders such as celiac disease, systemic sclerosis and post-intestinal resection state. Investigating changes in PYY in gastrointestinal diseases/disorders could be beneficial in clinical practice, where a receptor agonist or an antagonist can be used as a drug, depending on the condition. Similar to other neuroendocrine peptides/amines of the gut, PYY has broad physiological/pharmacological effects: it can bind to and activate several receptors with independent actions. Thus, in order to use PYY as a drug, receptor-specific agonists or antagonists need to be developed.

Gut hormones peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) play an integral role in appetite control and energy homeostasis. Entero-endocrine L-cells can be stimulated by nutrients and or bile acids to co-secrete PYY and GLP-1. The aim of this study was to determine the response of bile acids, PYY, GLP-1 and ghrelin after a test meal.

Twelve subjects with a BMI of 22·8 (0·52) kg/m² [mean (SEM)] received a 400 kcal test meal after which blood samples were taken every 30 min from 0 to 180 min. PYY, GLP-1 and ghrelin were measured by radioimmunoassays. Fractionated bile acids were measured by HPLC-MSMS.

PYY positively correlated with glycochenodeoxycholic acid (GCDCA) (rs = 0·23, P = 0·03) and taurochenodeoxycholic acid (TCDCA) (rs = 0·26, P = 0·02). GLP-1 positively correlated with GCDCA (rs = 0·22, P = 0·047) and glycodeoxycholic acid (GDCA) (rs = 0·3, P = 0·005). Ghrelin negatively correlated with GDCA (rs = -0·45, P≤ 0·0001), TCDCA (rs = -0·23, P = 0·034) and taurodeoxycholic acid (TDCA) (rs = -0·44, P≤ 0·0001).

PYY and GLP-1 responses correlated with chenodeoxycholic acid (CDCA) counterparts, whereas ghrelin negatively correlated with deoxycholic acid (DCA) counterparts. Specific bile acids may thus differentially affect entero-endocrine cells.

The administration of stimuli to the ileum inhibits upper gastrointestinal motility. The aim of this study was to determine whether a total colectomy can alter this motor inhibitory effect.

Beagle dogs were each equipped with four strain gauge force transducers on the upper gastrointestinal tract. The infusion of nutrients (saline as placebo control, oleate, butyrate, and glucose) began 90 min after feeding and continued for 30 min via a silicone catheter placed in the ileal lumen. Capsaicin (10 mg) was injected into the ileum as a bolus. All of the dogs underwent a relaparotomy and a total colectomy, and the same experiments were performed on all dogs.

Before performing a colectomy, the oleate, the glucose, and the capsaicin were each found to inhibit the postprandial upper gastrointestinal motility in comparison to the placebo control (P < 0.05). The butyrate had no inhibitory effect. After a total colectomy, the inhibition of upper gastrointestinal motility was observed after the intraileal infusion of the oleate and the capsaicin (P < 0.05). The motor inhibitory response to the intraileal glucose was delayed after a total colectomy, and a reduction of the motility index was not observed in the gastric antrum and the duodenum because of this delay. However, a significant reduction in the motility index was observed in the jejunum.

The intraileal stimuli-induced motor inhibition decreased after a total colectomy after the administration of glucose, but not after the administration of either oleate or capsaicin.

To investigate how the gastrointestinal transit function changes after ileal J pouch-anal anastomosis (IPAA) for ulcerative colitis (UC) and to study whether gastrointestinal transit time (GTT) has an influence on daily stool frequency, we investigated the relationship between GTT and stool frequency per day.

Forty patients with UC who had undergone restorative proctocolectomy, with ileostomy closure at least 48 to 120 months (mean 96.3) previously, and who had no preoperative and postoperative complications were recruited. They were divided into two groups on the basis of their stool frequency: 26 patients had a stool frequency of less than 6 times per day (group A: 16 men, 10 women; aged 15 to 59 years old, average 36.6) and 14 patients had a stool frequency of 7 or more times per day (group B: 10 men, 4 women; 24 to 56 years old, average 40.9). The GTTs using a radiopaque marker were studied. Interviews concerning the defecation states were performed at the examination.

High nocturnal stool frequency was significantly noted more in group B than in group A (P <0.001). All cases in group A and 12 cases in group B could discriminate flatus from feces, and there were significant differences between groups A and B (P <0.05). Feeling of stool remaining was significantly noted more in group B than in group A (P <0.01). Stool consistency in group A was harder than that in group B (P <0.001). Patients with soiling were significantly noted more in group B compared with those in group A (P <0.001). Incontinence was detected in only 2 cases in group B. Group A showed a better defecation state than group B. In the GTT study, the GTT was almost the same in groups A and B. The small bowel transit, pouch transit, and whole gut transit times in group B were faster than those of group A (P <0.001). Removal length of the terminal ileum in patients after IPAA: patients in group B (13.8 +/- 3.9 cm) had significantly more ileum removed compared with patients in group A (6.3 +/- 2.4 cm; P <0.001). Regression lines in the relationship between removal length of the terminal ileum and individual stool frequency showed there was a correlation between removal length of the terminal ileum and individual stool frequency per day in direct proportion (r = 0.79, P <0.001). A resection of more ileum, up to 15 cm, plays a role in increased stool frequency.

The present results suggested that rapid transit of both the small bowel and pouch may lead to a high stool frequency of 7 or more times per day with a poor defecation state after IPAA. It was also pointed out in this study that an important point is a resection of more ileum, up to 15 cm, plays a role in increased stool frequency.

PYY is a gastrointestinal hormone, mainly released from the distal intestine in response to intraluminal nutrients or via a neurohormonal pathway originating in the proximal intestine. Although there are several molecular forms of circulating PYY with different bioactivity, and further more than six subtypes of Y-receptors, the function is essentially inhibitory to digestive organs located upstream of the digestive tract. These inhibitory mechanisms are named jejunal, ileal and colonic brakes, and play an important supplementary role in adaptation following intestinal resection. When massive resection of the small intestine is performed, the release of PYY from the distal intestine increases, suppressing gastric acid secretion and motility of the gastrointestinal tract, and stimulating pancreatic secretion. After total colectomy, PYY release is reduced first due to reduction of PYY-containing cells, then gradually increases with time, contributing to adaptation of the digestive organs to the new condition.

The changes in PYY in several gastrointestinal disorders and their possible clinical implications are reviewed. The changes in PYY seem to be an adaptive response to alterations in the patho-physiological condition caused by the disease. This becomes evident in gastrointestinal disorders such as diabetes gastroenteropathy, inflammatory bowel diseases, celiac disease, systemic sclerosis and post-intestinal resection state. On the other hand, changes in PYY in chronic idiopathic slow transit constipation appear to be primary and could be one of the etiologic factors of the disease. PYY does not seem to be involved in colorectal carcinoma. Although gastrointestinal dysmotility in neuro-muscular diseases is evident, PYY is not affected. The changes in PYY in gastrointestinal disorders could be beneficial in clinical practice. Thus, in cases where an increase or decrease in PYY is desirable, a diet that increases or decreases PYY synthesis and release can be followed, or a receptor agonist or antagonist can be utilized.

In the last two decades, multiple aspects of the peptide YY (PYY) secretion have been investigated. Besides fat and fatty acids, many luminal nutrients in the distal intestine appear to induce PYY release. Some studies have shown that bile acid, but not nutrients, plays a crucial role in the regulation of PYY secretion. Moreover, chyme in the proximal intestine also regulates the peptide release by indirect action through humoral and neuronal factors. Gastrin, cholecystokinin, and the vagus nerve are major candidates for mediators of these indirect actions. Several growth factors have been shown to regulate PYY synthesis in mucosa of the distal intestine. This review is aimed at presenting an overview of these recent studies on PYY secretion in the distal intestine.

Restorative proctocolectomy with ileal pouch anal anastomosis (IPAA) has become the standard surgical procedure for ulcerative colitis (UC). The purpose of this study was to determine which factors are important to achieve good anal continence after IPAA in terms of the motor activity and pressure-volume relationship. A total of 17 patients with UC who underwent IPAA were evaluated. The internal ileal pouch pressure was transanally measured with and without volume-loading of the pouch which induces the urge to evacuate. The maximum tolerable volume (MTV), first urge volume (FUV), and ileal pouch compliance were calculated and the internal ileal pouch pressure records were subjected to spectral analysis for intensive evaluation of the intraluminal pressure waves. The FUV, correlation of the compliance of the FUV with MTV, and the remaining volume up to the MTV (RVMTV) were analyzed. Compliance of the FUV was significantly correlated with the RVMTV (r = 0.736, P < 0.01). The frequency of the phasic waves in the pouch decreased with length of follow up, reflecting improved function (r = -0.588, P < 0.05). The findings of this intensive analysis of manometric measurement indicate that the key factors in postoperative pouch function are RVMTV and the frequency of phasic waves in the W-pouch.

Reconstructing the enteric tract after near-total proctocolectomy by interposing a jejunal pouch between the distal ileum and the distal rectum slows small intestinal transit and decreases the number of stools per day compared to a conventional ileal pouch-distal rectal reconstruction. Our hypothesis was that the jejunal pouch operation brings about these results by protecting the ability of the ileal mucosa to secrete peptide YY, thus augmenting the hormonal ileal brake on small intestinal transit and decreasing the stool frequency. In five jejunal pouch dogs and five ileal pouch dogs, more than 6 months after the operation, serum peptide YY concentrations were determined before and at 30-minute intervals for 180 minutes after a standard meal. Fasting serum concentrations of peptide YY, measured by radioimmunoassay, were greater in jejunal pouch dogs (mean +/- SEM, 1340 +/- 143 pg/ml) than in ileal pouch dogs (804 +/- 52 pg/ml; P < 0.01). Postprandial peptide YY concentrations in jejunal pouch dogs were also greater at 30 minutes (jejunal pouch = 1524 +/- 131 pg/ml, ileal pouch = 913 +/- 67 pg/ml; P = 0.01) and 60 minutes after the meal (jejunal pouch = 1723 +/- 250 pg/ml, ileal pouch = 1001 +/- 70 pg/ml; P = 0.05) and peaked sooner (jejunal pouch = 81 +/- 17 minutes, ileal pouch = 147 +/- 12 minutes; P = 0.01). We concluded that the jejunal pouch operation results in greater ileal fasting and postprandial secretion of peptide YY than the ileal pouch operation. The greater release may account, in part, for the slower small bowel transit and decreased number of stools after the jejunal pouch operation.

Colonic fermentation of carbohydrate has been shown to influence gastric and intestinal motility. Our aim was to investigate the effects of colonic infusion of lactose and short-chain fatty acids (SCFAs) on lower esophageal sphincter (LES) function in humans. LES pressure (LESP), transient relaxations of LES (TLESRs), and esophageal pH were monitored over 6 h on 4 different days in 7 healthy volunteers. After 1 h of baseline recording, the effects of different colonic infusions (270 ml of isotonic or hypertonic saline, 30 g lactose, or 135 mmol SCFAs) were tested in fasting conditions and after a standard meal. Peptide YY (PYY) and oxyntomodulin (OLI) were also measured in plasma. Both lactose and SCFA infusions increased the number of TLESRs as well as the proportion of TLESRs associated with acid reflux episodes, but saline solutions did not. The postprandial fall of LESP was enhanced by previous SCFA infusion. Plasma PYY and OLI increased similarly after all colonic infusions. Colonic fermentation of lactose markedly affected LES function, and this effect was reproduced by SCFA infusion. Whether the mechanisms of this feedback phenomenon are of hormonal nature, neural nature, or both remains to be determined.

Our hypothesis was that a jejunal pouch used as a rectal substitute after proctocolectomy would slow enteric transit, delay defecation, and decrease stool frequency compared to an ileal pouch so used. Twelve dogs underwent proctocolectomy; six had a jejunal pouch-distal rectal anastomosis and six had an ileal pouch-distal rectal anastomosis. After recovery, postprandial mouth-to-anus transit was slower in jejunal pouch dogs (253 +/- 18 minutes [mean +/- SEM]) than in ileal pouch dogs (112 +/- 7.9 minutes; P <0.05). Moreover, jejunal pouch dogs passed only 4.1 +/- 0.3 stools during the 12 hours after eating, whereas ileal pouch dogs passed 6.3 +/- 0. 9 stools (P <0.05). The mean frequency of proximal ileal pacesetter potentials after feeding was less in jejunal pouch dogs (12 +/- 0.4 cycles/min) than in ileal pouch dogs (16 +/- 0.3 counts/min; P = 0. 01), and jejunal pouches had more action potentials (jejunal = 82% +/- 4.3% of pacesetter potentials had action potentials, ileal = 61% +/- 3.0%; P <0.05). In contrast, gastric emptying and pouch motility, emptying, mucosal integrity, and bacteriologic and histologic properties were similar in the two groups of dogs. We concluded that the jejunal pouch operation slowed enteric transit, delayed defecation, and decreased postprandial stooling compared to the ileal pouch operation.

The pathophysiology following a total colectomy with ileal pouch-anal anastomosis (IPAA) has not been sufficiently clarified yet. We investigated bile acid metabolism, bacterial bowel flora and transit of the alimentary tract after IPAA, with reference to administration of ursodeoxycholic acid (UDCA) in dogs undergoing IPAA. Ten adult beagle dogs underwent IPAA at one stage, and were observed for 12 months. UDCA (100 mg/day) was administered orally to five dogs, and the other five did not. In the UDCA(+) group, UDCA replaced other bile acids, especially cholic acid, accounting for 16.5% of gallbladder bile at 12 months after surgery. Both plasma levels and postprandial increase of total bile acids remained unchanged in the UDCA(+) group, but decreased in the UDCA(-) group at 12 months. Fecal excretion of bile acids tended to be smaller in the UDCA(+) group, and the ratio of secondary to primary bile acids was larger in the UDCA(-) group. Almost all the bile acids were in free form in stool, and UDCA constituted 19% in the UDCA(+) group. The transit time of the whole alimentary tract was elongated by administering UDCA, especially at an early period after IPAA. Although both anaerobic and aerobic bacteria decreased after IPAA, the latter decreased more in stool, resulting in an increase in the ratio of total anaerobes/total aerobes, especially in the UDCA(-) group. The decrease in Bacteroidaceae and Lactobacillus after IPAA was slightly smaller in the UDCA(+) group. Administration of UDCA following IPAA was efficient to induce rapid intestinal adaptation and also to keep the bile acid fraction in the ileal pouch less harmful.

The ileostomy model is considered to be a reliable model to reflect small bowel absorption. Studies in ileostomy subjects have shown that inulin and oligofructose pass through the small bowel without degradation and without influencing the absorption of nitrogen, fat, starch, calcium, magnesium or zinc. Inulin and oligofructose do not have any considerable effect on cholesterol absorption or bile acid excretion.

Mainly because of the loss of reservoir function, loss of sphincter function, and exclusion of the duodenal route, patients who undergo gastrectomy suffer from many adverse effects postoperatively. The ileocecal interpositional graft is an attractive method to use as a gastric substitute after gastrectomy and distal esophagectomy. A pedunculated ileocecal graft is placed between the esophagus and the duodenum. The cecum acts as a reservoir while the ileocecal valve protects against enteroesophageal reflux. The duodenal passage is also preserved. Fourteen patients underwent this operation. The technique-related morbidity was low and the quality of life was good. During a mean follow-up of 6 months, no evidence of severe dumping syndrome or reflux esophagitis was observed. Further prospective randomized studies are warranted to compare this technique with the standard methods of gastric reconstruction.

Peptide YY (PYY) is a gut hormone produced by endocrine cells in the distal small bowel, colon, and rectum. PYY inhibits upper gastrointestinal secretory and motor functions. The aim of this study was to determine whether basal and postprandial plasma PYY levels in patients with proctocolectomy and ileal pouch-anal anastomosis (IPAA) are reduced and to determine the relationship between plasma PYY and plasma cholecystokinin (CCK) levels.

Plasma concentrations of PYY and CCK were measured before and after ingestion of a standardized breakfast in 14 IPAA patients and in 12 healthy control subjects.

Basal PYY was slightly lower in the IPAA patients than in the controls (8.3 +/- 0.3 versus 9.3 +/- 1.1 pM; not significant). Ingestion of the meal induced a small but significant increase of PYY to a maximum of 10.9 +/- 0.9 pM in patients. Integrated postprandial PYY was markedly reduced in patients when compared with the controls (1725 +/- 66 pM*180min versus 3194 +/- 480 pM*180 min; P < 0.005). Plasma PYY concentrations were inversely correlated with plasma CCK concentrations in the 2nd and 3rd h after the meal (r = -0.86; P = 0.0001).

PYY release in response to meal ingestion is markedly reduced but not completely absent in patients with proctocolectomy and ileal pouch-anal anastomosis. The inverse relationship between circulating PYY and CCK in the late postprandial phase is compatible with a negative feedback regulation of CCK release by endogenous PYY.

This study evaluates peptide tyrosine-tyrosine (PYY), intestinal transit, fecal retention time, and anal sphincter manometry in colectomized patients with ileal pouch-anal anastomosis.

Plasma and pouch PYY, mouth-to-pouch transit time, fecal retention time, and anal canal pressures were studied in 27 patients with ileoanal pouches a mean of 50 (range, 3-84) months after loop ileostomy closure.

Basal and peak postprandial plasma PYY were significantly reduced in patients with pouches compared with controls (P < 0.0001). Pouch PYY was decreased compared with control ileal PYY (P = 0.0003). No significant correlation was noted between intestinal transit and total integrated PYY response in patients with pouches (r=0.36; P=0.06). Fecal retention time was related to postprandial total integrated response of plasma PYY (r=0.43; P=0.02), mouth-to-pouch transit (r=0.87; P < 0.0001), and resting (r=0.44; P=0.02) and squeeze (r=0.62; P=0.0006) anal sphincter pressures.

Colectomized ileoanal patients with pouches showed decreased plasma and pouch PYY compared with controls. Intestinal transit was not significantly related to PYY release. However, prolonged pouch fecal retention was associated with greater PYY release, mouth-to-pouch transit, and anal sphincter pressures.

We have previously described a negative feedback loop that inhibits duodenal motility when nutrients are infused into the ileum and colon. In the present study, we examined the role of extrinsic innervation and plasma levels of peptide YY (PYY) in mediating this phenomenon. We perfused neurally intact (n = 5 dogs) or extrinsically denervated (n = 6 dogs) isolated loops of proximal colon with isomolar NaCl or a mixed-nutrient solution at 2 and 6 ml/min for 4 h during fasting or for 2 h beginning 15 min after a meal. Both rates of infusion with NaCl prolonged the cycle length of the duodenal migrating motor complex (MMC) in the group with neurally intact loops but not in the group with extrinsically denervated loops. Nutrient infusions increased the MMC cycle length in both groups. Integrated plasma concentrations of PYY were increased by nutrients but not by NaCl in both groups. These data suggest that increased volumes and unabsorbed nutrients in the proximal colon alter proximal small bowel motility. Volume-induced effects are mediated via extrinsic nerves, whereas nutrient-induced effects may be mediated by humoral factors, such as plasma PYY.

We have recently described a reservoir for rectal replacement after total mesorectal excision for rectal carcinoma. The ileocecal segment with its intact extrinsic nerve and blood supply is placed between the ascending colon and the anal canal. This reconstruction has been shown to provide good defecation quality and anorectal function. Whether gastric emptying and small as well as large bowel transit are affected by this transposition remains unclear. Our aim was to quantify whole gut transit in such patients and compare it with that of a matched group of controls.

Gastric emptying rates and small intestinal and colonic transit times were assessed scintigraphically in 12 patients aged 46 to 87 years with ileocecal reservoir reconstruction after total mesorectal excision and compared to a sex-matched group of asymptomatic healthy volunteers of similar age. Gastric emptying rates and small intestinal and colonic transit times were calculated as described previously. Data were compared using Wilcoxon's signed rank test for gastric emptying rates and small bowel transit or by analysis of variance for colonic transit; p < 0.05 was considered significant.

Gastric time for half of the meal (T50) was 161 +/- 16 minutes for patients and 201 +/- 22 for the controls. Small bowel transit time was 150 +/- 15 minutes for patients and 177 +/- 22 for the controls. Geometric center at 6 hours was 1.53 +/- 0.13 for patients and 1.27 +/- 0.16 for the controls. Geometric center at 24 hours was 2.96 +/- 0.23 for patients and 2.57 +/- 0.25 for the controls. Data are mean +/- SEM.

Gastric emptying rates and small bowel transit and colonic transit times (expressed as geometric center at 6 and 24 hours) were similar in patients with ileocecal reservoir reconstruction and in a sex- and age-matched group of healthy controls. We conclude that the transposition of an ileocecal segment with intact extrinsic neurovascular supply between the sigmoid colon and the anal canal does not alter whole gut transit, not even in any of the presumably key regions.

The physiologic role of the colon as an endocrine organ is not clear. We therefore studied the enteroinsular axis in patients with ulcerative colitis after colectomy.

The subjects included 11 patients with a conventional ileostomy, 10 patients with an ileoanal reservoir, and 10 normal controls. The concentrations of glucose, insulin, gastric inhibitory peptide (GIP), and glucagon-like peptide-I (GLP-I) were measured in plasma during an oral glucose test.

The peak level of glucose and peak levels and area under the curve (AUC) of insulin and GIP were higher in patients (P < 0.05). Neither the peak level nor the AUC of GLP-I differed between patients and controls, but time to peak level was four times longer in patients with an ileoanal reservoir (P < 0.05).

Colectomy seems to affect the enteroinsular axis, leading to hyperinsulinemia and an impaired glucose tolerance. Moreover, patients with an ileoanal reservoir have a slower GLP-I response after intake of glucose.

Capsaicin is known to contract smooth muscles and to have an excitatory action on thin, primary afferent neurons. The aim of this study was to test the hypothesis that intragastric capsaicin may have an excitatory effect on colonic motility.

Mongrel dogs equipped with five strain-gauge force transducers on the colon (C1-C5) were used. In 5 dogs, the effect of intragastric capsaicin (0.05, 0.1, 0.3, and 0.5 mg/kg) on colonic motility in the presence or absence of the cholinergic blockers atropine and hexamethonium was studied. In 4 dogs, the effect of capsaicin (0.5 mg/kg) administration into a vagally innervated or denervated gastric pouch on colonic motility was investigated.

Motility at C2-C3, C1-C3, and C1-C5 was significantly increased by 0.1, 0.3, and 0.5 mg/kg of capsaicin, respectively. The excitatory effect of capsaicin on colonic motility was inhibited by atropine and hexamethonium. Colonic motility at C1-C4 was significantly increased by capsaicin administration into a vagally innervated pouch but was not affected by capsaicin administration into a vagally denervated pouch.

These results indicate that intragastric capsaicin predominantly stimulates motility in the proximal half of the colon through neural pathways, probably through a vagovagal reflex, but sympathetic involvement cannot be excluded.

We wanted to clarify whether the postprandial intestinal feedback control activated by nutrients in the distal gut exerts different effects on motility, transit of digesta, and absorption of nutrients in the proximal gut. Additionally, interrelationships among motility, transit, and absorption were to be elucidated because these relationships have only been investigated in the fasted state. In five minipigs, a 150-cm segment of the proximal jejunum was isolated by two cannulas. Motility of the jejunal segment was recorded by multiple strain gauges and analyzed by computerized methods. Markers (Cr- and Cu-EDTA) were used for the measurement of the flow rate, transit time, and absorption of nutrients. After a meal, the test segment was perfused with 2 kcal/min of an elemental diet over a period of 90 min. A feedback inhibition was activated by infusion of nutrients into the midgut at rates of 1-4 kcal/min. Saline was infused as control. With increasing energy loads infused into the midgut, the motility index and the length of contraction waves decreased, whereas the incidence of stationary contractions increased, ie, the motility changed from a propulsive to a segmenting pattern. These modulations of motility were associated with a linear decrease in the flow rate and a linear increase in transit time. Flow and transit were linearly correlated with each other. Additionally, the reduction in flow rate and the delay in luminal transit were associated with a linear increase in the absorption of nutrients. However, the increase in absorption induced by the feedback mechanism was small (7.3-13.4%) compared to the marked inhibition of the motility parameters (54-64%), the flow rate (59%), and the delay of transit (5.8-fold). Feedback control primarily modulated motor patterns and luminal flow, whereas the small increase in absorption was only a side effect due to the longer contact time of the nutrients with the mucosa.

The aim was to study and compare the passive biomechanical wall properties in the isolated duodenum and distal ileum of the guinea pig in vitro. The organ bath contained a Krebs-Ringer solution with 10(-2) M MgCl2 to abolish smooth muscle contractile activity. Stepwise inflation of an intraluminal balloon, in which the cross-sectional area (CSA) was measured, provided the distension stimulus. The circumferential wall tension-strain distributions and wall stiffness-strain relations were computed from steady-state values of these measurements in order to evaluate the passive elastic properties. The CSA always reached equilibrium within the 2-min distension period. The CSAs obtained in the distal ileum were higher than those in the duodenum (P < 0.001). The basal CSA was 17.31 +/- 1.14 mm2 and 12.96 +/- 0.42 mm2 for the distal ileum and the duodenum, respectively (P < 0.01). At a maximum pressure of 6 kPa, the CSA of the ileum was 56.63 +/- 1.81 mm2 and 36.86 +/- 1.76 mm2 for the duodenum (P < 0.01). The circumferential wall tension-strain distributions showed an exponential behavior that accorded well with the equation Y = exp(a+bX) with determination coefficients of 0.96 +/- 0.01 and 0.99 +/- 0.00 in the duodenal segments in the distal ileal segments, respectively. The values of a (intercept with the y-axis) were 0.54 +/- 0.11 and -0.35 +/- 0.19 for the duodenal and ileal segments, respectively (P < 0.001). The slope of the curves (b values) were 4.34 +/- 0.35 in the duodenal and 5.23 +/- 0.37 in the ileal segments (0.1 > P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Proctocolectomy with ileal pouch-anal anastomosis is the surgical treatment of choice for severe chronic ulcerative colitis and familial polyposis coli because the entire colonic mucosa is removed while anal function can be preserved and the necessity for permanent ileostomy is eliminated. Long-term functional results are generally gratifying, as defecation frequency and degree of incontinence are acceptable in most patients. Pouchitis, however, a non-specific inflammation of the ileal reservoir, is a major long-term complication occurring in a considerable number of patients. The etiology of pouchitis is unknown. Since pouchitis occurs more frequently or even exclusively in ulcerative colitis patients it is assumed that pouchitis is a novel manifestation of inflammatory bowel disease. However, bacterial overgrowth in the ileal pouch may also play a pathogenetic role. Chronic inflammation and villous atrophy of varying severity is found in virtually all pouches. Acute inflammatory changes and ulceration are associated with pouchitis.

To determine the effect of ileal oleate on fasting intestinal motility, pairs of duodenal and ileal catheters and bipolar duodenal and jejunal seromuscular electrodes were surgically implanted in six dogs. The ileum was perfused with either normal saline (154 mM NaCl) or oleic acid emulsion (152 mM), while intestinal myoelectric activity was continuously monitored. For transit studies, a bolus of [3H]PEG was injected into the duodenum, and jejunal and ileal alliquots were collected every 15 min for a 6-hr study period. Plasma samples were collected for radioimmunoassays of peptide YY and enteroglucagon. Ileal oleate infusion increased the MMC cycle length and decreased the number of MMCs (P < 0.001) and the myoelectric spike-burst frequency/10 min in the duodenum (P < 0.05). Both duodenal-jejunal (P < 0.05) and duodenal-ileal transit (P < 0.01) were delayed markedly by ileal perfusion with oleic acid emulsion as compared to control studies. Ileal oleate increased plasma levels of peptide YY (P < 0.01) and enteroglucagon (P < 0.01). Ileal perfusion with oleate therefore activated the so-called "ileal brake," diminishing duodenal myoelectric spike bursts and slowing intestinal transit while concurrently increasing plasma levels of peptide YY and enteroglucagon.

As a result of improved understanding of the origin and control of motility at both the whole organ and the cellular level, a scientific approach to the diagnosis and treatment (both medical and surgical) of motility disorders has evolved. Examples are present for all levels of the gastrointestinal tract. Manometric, myoelectric, and pharmacologic studies have elucidated the role of the lower esophageal sphincter and stomach in the pathogenesis of gastroesophageal reflux and determined the mechanism of successful medical and surgical treatment. Better evaluation of colorectal motility using colonic transit studies, pelvic floor radiography, and rectoanal manometrics has led to a better identification of both the etiology of severe constipation and patients who will have a successful surgical outcome. Studies of normal and abnormal gallbladder motility and responsiveness to hormonal stimulation have shed light on the cellular abnormalities in gallbladder myocytes that predispose to gallstone formation. Finally, since we have learned that certain surgical procedures affect motility in an adverse manner, a better basic understanding of gastrointestinal physiology has led to a better clinical understanding of the mechanism by which the changes occur and to the development of more directed physiologic operations. The classic example is seen in ulcer surgery, where the introduction of highly selective vagotomy instead of truncal vagotomy preserved antral innervation and decreased the incidence of postvagotomy complications. All these concepts and more are addressed in more detail in subsequent articles in this issue.

Ileal pouch-anal anastomosis cures chronic ulcerative colitis with an acceptable perioperative morbidity and mortality. The great majority of patients achieve satisfactory continence with an excellent quality of life. However, continence is not perfect, and fecal soilage is a troublesome problem for a small number of patients. Moreover, as many as one third of patients develop pouchitis, for which an effective means of long-term prevention or treatment has yet to be developed. Finally, controversial issues such as optimal pouch design or technique of anastomosis will be resolved only when long-term follow-up of randomized trials has been completed.

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.

Upper gastrointestinal motility is regulated by the presence of nutrients in the distal gut. The present study evaluated whether lipid-induced ileal brake on gastric emptying (1) can be elicited by low fat concentrations; (2) is a dose-dependent phenomenon; and (3) is related to gastrointestinal peptide release.

Seven patients were studied in the defunctionalized stage of total colectomy, on three separate occasions. On each study day, patients ate a meal labeled in the solid component; 30 minutes later, one of the following solutions was randomly infused into the ileal pouch: 0.9% saline, 2% oleic acid, and 20% oleic acid. Plasma concentrations of peptide YY (PYY), enteroglucagon, neurotensin, and motilin were measured.

Both oleic acid solutions slowed gastric emptying compared with saline (P < 0.001), the effect being dose dependent (P < 0.001). Ileal infusions did not modify neurotensin and enteroglucagon levels but induced a dose-dependent increase of PYY (P < 0.01) and a borderline decrease of motilin (P = 0.05) levels. Slower rates of gastric emptying were related to increased plasma concentrations of PYY (r = 0.615; P < 0.05).

This study shows that (1) the ileal brake on gastric emptying can be evoked by low doses of lipids in the distal ileum; (2) the delay of gastric emptying is related to the release of PYY; and (3) both phenomena are dose dependent.

Colectomy and endorectal ileal pull-through with ileal reservoir (PTR) have become a standard operative procedure for severe ulcerative colitis and familial polyposis coli. Satisfactory results have been reported with a number of different reservoir designs; however, the optimal reservoir size and configuration remain controversial. Two groups of five dogs each, undergoing colectomy and PTR with construction of either 5-cm-long or 18-cm-long lateral ileal reservoirs, were studied to compare defecatory patterns, intestinal transit, and reservoir emptying. Three months postoperatively, dogs with long ileal reservoirs demonstrated a higher stool frequency and made more unsuccessful attempts at defecation. Evacuation of viscous polyethylene glycol solution from the long reservoirs was prolonged during the first hour compared with short reservoirs. Two of the five long reservoirs showed mucosal ulcerations on postmortem examination, whereas none were present in any of the short pouches. Increases in stool water content and subsequent reduction of urine volumes as well as a prolongation in oroanal transit times occurred to a similar degree in both groups. It is concluded that short lateral isoperistaltic reservoirs empty more effectively than do long reservoirs.

A study was carried out to evaluate the breath hydrogen test as a method of estimating small bowel transit in patients with an ileal pouch and to determine whether gut transit time influenced functional outcome. Twelve patients with an ileal reservoir and ten control subjects ingested a test meal of 400 ml chicken soup, 20 g lactulose and 50 ml dilute barium solution. Concurrent breath hydrogen testing and radiological screening was carried out until the head of the test meal reached the ileal pouch or caecum. At the time that the test meal arrived in the pouch, faecal anaerobic bacterial counts were obtained. Pouch compliance, functional capacity and anal sphincter pressures were also measured. While there was an excellent correlation between radiological and breath hydrogen measures of orocaecal transit time in controls (P less than 0.001), no such relationship was found for oropouch transit. Four of the 12 patients with a pouch produced no hydrogen after test meal ingestion, while in two other such patients breath hydrogen peaks occurred when the head of the meal was in the jejunum. The magnitude of the breath hydrogen rise in patients with an ileal pouch correlated well with faecal anaerobic bacterial counts (P less than 0.01). The median (95 per cent confidence interval) radiological small bowel transit time was more rapid in patients with a pouch than in control subjects: 28 (23-33) versus 72 (46-86) min (P less than 0.01). Increased 24-h frequency of defaecation was associated with more rapid small bowel transit after ileal reservoir construction (P less than 0.01) but correlated with neither pouch capacity nor compliance. These data show that small bowel transit time may be a determinant of ileal pouch function but that breath hydrogen estimation of gut transit time in patients with an ileal reservoir is unreliable.

Three anal sphincter-saving operations--ileorectostomy, ileal pouch-anal anastomosis, and ileal pouch-distal rectal anastomosis--are currently being used in the surgical treatment of chronic ulcerative colitis. All three operations remove the disease, or most of it, and yet they maintain transanal defecation, reasonable fecal continence, and a satisfactory quality of life. All three avoid permanent abdominal ileostomy. Ileorectostomy is the easiest to perform, but it leaves residual disease in the remaining rectum and proximal anal canal that may cause symptoms and that may predispose the patient to cancer. In contrast, ileal pouch-anal anastomosis, although a more technically demanding procedure, totally eradicates the colitis. Its main drawbacks--frequent stooling, nocturnal fecal spotting, and pouchitis--are usually satisfactorily treated with loperamide hydrochloride and metronidazole. Ileal pouch-distal rectal anastomosis is somewhat easier to perform than ileal pouch-anal anastomosis and may result in less nocturnal fecal spotting. Like ileorectostomy, however, the operation leaves residual disease in the distal rectum and proximal anal canal. Considering all of these factors, the ileal pouch-anal operation is preferred today for most patients who require surgery for chronic ulcerative colitis.

Endoscopic retrograde sphincterotomy was performed on four sedated pigs, ages 3-4 months, using a standard human duodenoscope and papillotome. Sphincterotomies, 1 cm in length, were well-tolerated, and all animals recovered promptly, spontaneously regained gastrointestinal function, and gained weight. The first three animals were sacrificed after one week, and autopsy revealed no complications. The fourth animal was sacrificed immediately following the procedure, and no evidence of perforation was found. These observations demonstrate that the pig is a valid experimental model for endoscopic sphincterotomy. Its use in training is limited by technical and anatomic differences from humans. Potential uses of this technique in research are discussed.