Gastrointestinal hormones in short bowel syndrome. Peptide YY may be the 'colonic brake' to gastric emptying.

BACKGROUND: 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. AIMS: 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. SUBJECTS: 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. METHODS: The subjects all consumed a 640 kcal meal; blood samples were taken for 180 minutes for measurement of gastrointestinal hormones. RESULTS: 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. CONCLUSIONS: 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'.     

Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome

OBJECTIVES: Irritable bowel syndrome (IBS) and dyspepsia often overlap. Delayed gastric emptying has been reported in IBS patients, although conflicting results exist. Whether overlapping dyspepsia correlates with gastric emptying abnormalities in IBS patients has not been clarified. This study aimed to evaluate gastric emptying of solids and its relationship with dyspeptic symptoms in IBS patients. METHODS: A total of 146 IBS outpatients seen in a referral center were evaluated for dyspeptic symptoms using a validated questionnaire. Gastric emptying of solids was evaluated scintigraphically in all patients and in 50 healthy controls. RESULTS: Overlapping dyspepsia was diagnosed in 96 (66%) IBS patients. On average, gastric emptying rates were lower in IBS patients (mean +/- SEM, 33% +/- 1%/h) compared with controls (40% +/- 2%/h; p < 0.01). Specifically, gastric emptying was delayed in IBS patients with overlapping dyspepsia (31% +/- 1%/h; p < 0.01), whereas IBS patients without dyspeptic complaints showed gastric emptying rates (37% +/- 2%/h) that were similar to those of healthy controls (40% +/- 2%/h). Relevant postprandial fullness (OR = 4.7, 95% CI = 1.8-12.5) and relevant nausea (OR = 3.3, 95% CI 1.2-9.3) were independently associated with delayed gastric emptying. CONCLUSIONS: IBS patients without overlapping dyspepsia have normal gastric emptying of solids. A significant association exists in IBS patients between delayed gastric emptying and overlapping relevant postprandial fullness and nausea.     

肠易激综合征患者消化不良症状与胃排空之间的关系

目的　探讨肠易激综合征(IBS)患者消化不良症状与固体胃排空之间的关系。方法　采用不透X线标志物测定54例IBS患者餐后6小时残留胃内的钡条数,确定6种消化不良症状并对每种症状计分。结果　IBS患者中有消化不良症状者占54%,便秘型IBS患者与腹泻型IBS患者的消化不良症状总积分无明显差异(P>0. 05)。便秘型IBS患者中有消化不良症状者的固体胃排空延迟发生率较无消化不良症状者明显高(P<0. 05 ),腹泻型IBS患者中有消化不良症状者和无消化不良症状者的固体胃排空延迟发生率比较,无明显差异(P>0. 05);便秘型IBS患者的固体胃排空延迟发生率较腹泻型IBS高(P<0. 01)。结论　便秘型IBS患者消化不良症状与固体胃排空延迟可能相关,腹泻型IBS患者消化不良症状与固体胃排空延迟无关。     

Failure to demonstrate altered gastric emptying in irritable bowel syndrome

In irritable bowel syndrome (IBS), abnormalities of motility have been observed in the esophagus and small bowel, as well as in the colon. In order to investigate gastric function, gastric emptying has been measured in 25 patients with strictly defined IBS and compared with 25 age-and sex-mathched controls. A standard radioisotope method for measuring gastric emptying has been employed. There was no significant difference between the two groups (T1/2 gastric emptying, IBS subjects 99.3±9.4 min, control subjects 104.0±11.9 min, mean±sem), nor was there any major correlation between different symptom patterns and altered gastric emptying times. The results of the present investigation suggest that future studies on abnormalities in IBS should investigate other aspects of gastric motor function.     

Gastric emptying and dyspeptic symptoms in the irritable bowel syndrome.

Many patients with irritable bowel syndrome (IBS) have symptoms suggestive of disturbances in gastric emptying, but so far no abnormalities in gastric emptying have been demonstrated in these patients. We studied gastric emptying of a solid meal with a 99mTc-labeled pancake in 16 healthy volunteers (8 women and 8 men; age, 20-33 years; mean age, 25 years) and 16 predominantly constipated IBS patients (10 women and 6 men; age, 17-43 years; mean age, 25 years). The incidence and severity of the symptoms nausea, vomiting, early satiety, and pain in the upper abdomen were scored. The duration of the lag phase of gastric emptying of the solid meal did not differ between the groups (controls, 16.6 +/- 4.7 min; IBS patients, 22.2 +/- 14.7 min). In normal subjects lag phase duration and emptying rate were correlated (r = 0.49, p greater than 0.05); in the IBS patients they were not. Post-lag gastric emptying of the solid meal was slower (p less than 0.01) in the IBS patients (0.58 +/- 0.24%/min) than in the control subjects (0.85 +/- 0.24%/min). No correlations were found, however, between the emptying rate and the severity of the upper abdominal symptoms. This study is the first to demonstrate that gastric emptying is delayed in IBS patients. This abnormality, however, appears not to be the major determinant of the upper abdominal symptoms often present in these patients.     

High-fat diet in a short bowel syndrome

A patient with only 137 cm of jejunum suffereing from excessive jejunostomy losses was studied on three isocaloric liquid formula diets (3850 kcal/24 hr) differing only in carbohydrate and fat content. An increase in dietary fat from 64 g to 200 g per 24 hr and a reciprocal decrease in dietary carbohydrates resulted in a linear increase in the amount of fat absorbed, from 44 g to 133 g and in a 2.5-fold decrease in ostomy fluid bile acids. No undesirable side effects were noted on the 200-g fat diet: the ostomy fluid dry weight was lower than on 64 g of fat and the ostomy fluid output was lowest of all diets. Compared to healthy adults, the patient had higher fasting blood insulin and pancreatic glucagon. Meal-stimulated insulin, glucagon, gastrin, and GIP were also more than two standard errors above mean responses observed in healthy subjects. Smallest meal-stimulated increase in insulin, gastrin and GIP was noted on the 200-g fat diet. This diet induced the highest levels of glucagon. In a hormonally hyperactive individual after massive resection of the distal intestine favorable effects of a high-fat diet consist of increased absorption of dietary fat and bile acids and reduced release of gastroenteropancreatic hormones with the exception of glucagon.     

Enhancing bowel adaptation in short bowel syndrome

Malabsorption of both nonessential and essential nutrients, fluid, and electrolytes will, if not compensated for by increased intake, lead to diminished body stores and to subclinical and eventually clinical deficiencies. By definition, intestinal failure prevails when parenteral support is necessary to maintain nutritional equilibrium. After intestinal resection, adaptation, a progressive recovery from the malabsorptive disorder, may be seen. Research has focused on optimizing remnant intestinal function through dietary or pharmacologic interventions. In this review, factors responsible for the morphologic and functional changes in the adaptive processes are described. Results of clinical trials employing either growth hormone and glutamine or glucagon-like peptide-2 in short bowel patients are presented.     

The short bowel syndrome

The authors demonstrate on case-histories their experience with short-loop syndrome which develops after extensive resections of the small intestine. The clinical picture of the syndrome is characterized by diarrhoea, steatorrhoea, maldigestion and malabsorption with loss of body weight. Non-surgical treatment of the syndrome copies its different stages. The objective of conservative therapy is above all to preserve the nutritional integrity of the organism and gradual adaptation of the gut which will make eventually a change to oral intake possible. This adaptation takes 1 to 2 years. Last not least, treatment should eliminate the diarrhoea. The authors demonstrate on examples that properly conducted treatment prevented the development of malnutrition, contrary to another case where the sequelae of surgery were underestimated and the patient developed cachexia and pernicious anaemia.     

Disturbed gastric and small bowel transit in severe idiopathic constipation

Many patients with severe idiopathic constipation complain of upper gastrointestinal symptoms, and these often persist after subtotal colectomy. To determine if there is a disturbance of upper gastrointestinal motility in this condition, we have studied gastric emptying for solids (¹¹¹In-containing pancake) and liquids (^99mTc-containing orange, juice) for a longer period after a meal (6 hr) than in previously reported gastric emptying studies. Small bowel transit for solids was also measured. All patients had emptied their colon the day before the study. Twelve women (mean age 36 years) with a bowel frequency of less than once per week, proven slow intestinal transit, and a normal diameter colon were studied. Twelve healthy controls (eight female and four male, mean age 33) were also studied. As a group the constipated patients demonstrated no statistically significant delay in emptying during the first 3 hr, although the emptying rate for three of 12 individuals fell outside the normal range. However, at 6 hr after ingestion of the meal, six of 10 patients had residual gastric contents greater than normal-up to 48% solid residue (median: 11% for patients and 0% for controls,P<0.01) and 40% of liquid (median 9% vs 0%P<0.01). Three of four patients with upper gastrointestinal symptoms 6 hr after the meal had gastric retention of solids markedly outside the normal range (48%, 32%, and 16%; normal<4%). Small bowel transit time was assessed as the time for the solid phase to pass from the duodenum to the cecum; the constipated patients demonstrated delayed transit (median: 75 vs 55 min,P<0.01). Effectiveness of small bowel transit was assessed by the proportion of solids in the cecum at the time the stomach had emptied 50% of the solid meal; this was reduced in the patients (median: 6 vs 18%,P<0.01). All patients with normal gastric emptying had normal small bowel transit, and all those with delayed gastric emptying had prolonged small bowel transit. Colonic transit of the radioisotope was slow in all patients (head of the radioisotope column, cecum to stool, median: 96 vs 31 hr,P<0.01). Many patients with severe idiopathic constipation have a disturbance of gastric and small bowel transit that may be related to symptoms and that have implications for treatment.     

Predictors for short bowel syndrome in Crohn's disease

Background and aimPatients with Crohn's disease (CD) are at risk for short bowel syndrome (SBS). We investigated independent predictors for SBS in these patients to allow the development of preventive strategies.MethodsAll adult patients seen at the Nancy University hospital for CD or SBS between 2012 and 2019 were eligible for inclusion in this case-control study. Each CD patient with SBS was matched to 9 controls.Results410 CD patients were included (369 without SBS and 41 with SBS). Subjects with SBS underwent significantly more bowel resections (median value of 3 vs 1, p<0.0001) and median time before the first surgery was not different than controls (6 vs 4 years, p=0.59). A higher need for parenteral support was found in end-jejunostomy SBS than in jejunocolic and jejunoileal SBS (70.6% vs 25% and 0%, p=0.0031). Montreal B1 behavior (OR 0.02, CI 95% 0-0.08) and budesonide treated-patients (OR=0.03, CI 95% 0.003-0.2) were at lower risk of SBS, while IV steroid treated-patients were at higher risk (OR=8.5, CI 95% 3.0-24.9).ConclusionMontreal B1 behavior, IV steroids and budesonide use are influencing predictors for this complication. These predictors should be assessed in daily clinical practice to prevent SBS occurrence.     

Nutritional absorption in short bowel syndrome

Eight patients with a short bowel resulting from intestinal resection and clinically stable for at least one year were studied for 10 days. The diet chosen was lactose-free with a low fiber content and contained 22% of total calories as protein, 32% as carbohydrate, and 46% as fat. Total fluid volume was kept constant, and all patients were in positive nitrogen balance. During the 10-day period, blood chemical concentrations, stool, and/or ostomy volume, urine volume, electrolyte excretion, and calorie and divalent cation absorption were measured. In addition it was determined that fluid restriction during meals did not affect these parameters. In these patients the absorptions of fat, carbohydrate, protein, and total calories were 54%, 61%, 81%, and 62%, respectively. Similarly the absorption of the divalent cations, calcium, magnesium, and zinc, were 32%, 34%, and 15%, respectively. We suggest that patients with short bowel syndrome, who have been stable for at least one year and who can tolerate oral diets, do not need to restrict fat or to separate fluids from solids during their meals. Furthermore, they should increase their oral intake to 35–40 kcal/kg ideal body weight in order to counteract their increased losses. The diet should contain 80–100 g protein/day in order to maintain a positive nitrogen balance and a large margin of safety. In addition, these patients may take oral supplementation of calcium, magnesium, and zinc to maintain divalent cation balance.This work was supported by a grant from the Ontario Ministry of Health PR. 228.     

Intestinal microbiota in short bowel syndrome

Short bowel syndrome (SBS) is the main cause of intestinal failure especially in children. The colon is a crucial partner for small intestine adaptation and function in patients who have undergone extensive small bowel resection. However, SBS predisposes the patient to small intestine bacterial overgrowth (SIBO), explaining its high prevalence in patients with this disorder. SIBO may significantly compromise digestive and absorptive functions and may delay or prevent weaning from total parenteral nutrition (TPN). Moreover, SIBO may be one of the causes of intestinal failure-associated liver disease, requiring liver transplantation in some cases. Traditional tests for assessing SIBO may be unreliable in SBS patients. Management of SIBO with antibiotic therapy as a first-line approach remains a matter of debate, while other approaches, including probiotics, offer potential based on experimental evidence, though only few data from human studies are available.     

Amitriptyline absorption in a patient with short bowel syndrome

Oral drug therapy in patients with short bowel syndrome can be quite challenging. We report the case of a 40-yr-old woman with short bowel syndrome and depression requiring antidepressant drug therapy. After buccal administration of amitriptyline, therapeutic serum antidepressant concentrations were attained despite the patient having only 18 inches of proximal small bowel. Clinical improvement in mood was seen, with the only drug side effects being dry mouth and bitter drug taste. Buccal absorption likely is playing a major role in attaining therapeutic serum tricyclic antidepressants drug concentrations.     

Evidence for autonomic dysregulation in the irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common gastrointestinal disorder characterized by chronic abdominal pain and visceral hypersensitivity. In this study, resting blood pressure and heart rate were recorded in 20 IBS patients and 23 controls. We assessed pain intensity and unpleasantness to visceral and cutaneous stimuli using rectal distension and immersion of the foot in hot water. Mean resting heart rate was higher in IBS patients compared to controls. IBS patients rated pain intensity and unpleasantness to visceral and cutaneous stimuli significantly higher than controls. In IBS patients, blood pressure was significantly inversely associated with visceral pain and only weakly and positively associated with cutaneous pain; there were no relationships in controls. Sex and anxiety did not explain these relationships. In conclusion, we found evidence suggestive of central autonomic dysregulation in IBS patients.     

Severe short bowel syndrome with a surgically reversed small bowel segment

Summary We report a case of short bowel syndrome (60 cm of jejunum anastomosed to the left colon) with reversal of the distal 15 cm of jejunum in a 21-year-old man. The nutritional absorptive capacity and digestive motility was studied for 18 months postoperatively. His absorptive capacity reached subnormal values allowing him oral nutritive autonomy and normal social life. The results of the manometric study suggested that the reversed segment delayed intestinal transit time. The prolonged contact of the chyme with the intestinal absorptive mucosa possibly increased its absorptive capacity.Our data and the literature reports suggest that reversal of a bowel loop could help wean patients from their dependence on parenteral nutrition.     

Advances in the management of short bowel syndrome

Short bowel syndrome (SBS) is the predominant cause of intestinal failure and is thus associated with a high degree of morbidity and mortality. One of the reasons this occurs is the dramatic reduction in nutrient absorptive capacity. Of the many causes of SBS, the most common cause is extensive surgical resection. The impressive ability of the bowel to adapt functionally and morphologically is critical for decreasing morbidity and mortality in these patients. The degree of adaptation is vital in decreasing the dependence on parenteral nutrition (PN) and for improving patient quality of life and long-term outcome. Provision of appropriate and sufficient nutritional and fluid support is essential for the management of these patients. The primary goal is to prevent or eliminate the need for PN. Recent developments have promoted a greater understanding of the process of intestinal adaptation. Various intestinal trophic factors have been recognized. These efforts have led to the early development of hormonal therapy to stimulate intestinal adaptation and enhance intestinal absorption. Intestinal transplantation remains an option for those who have developed life-threatening complications from PN and cannot be managed using more conservative techniques.     

Energy absorption as a measure of intestinal failure in the short bowel syndrome.

Energy absorption from a liquid test meal, intestinal transit rate and water and sodium output over a six hour period were measured in five patients with an ileostomy and 12 patients with the short bowel syndrome, five of whom were on longterm parenteral nutrition. The proportion of total energy absorbed was greatest in the ileostomists (median 87%, range 82-92%), less in short bowel patients not on parenteral nutrition (median 67%, range 59-78%, p less than 0.01) and least in the short bowel group who needed it (median 27%, range 2-63%, p less than 0.01). Transit rate was more rapid in the short bowel patients compared with the ileostomists. A close correlation was observed between percentage energy absorption and the dry weight of the stools/stoma effluent collected during the six hour test period (r = -0.99, p less than 0.001). This simple non-invasive test quantitates the degree of intestinal failure and may be of practical help in management.