Small intestinal protein infusion in humans: evidence for a location-specific gradient in intestinal feedback on food intake and GI peptide release.

BACKGROUND: Protein infusion in the small intestine results in intestinal brake activation: a negative feedback mechanism that may be mediated by the release of gastrointestinal peptides resulting in a reduction in food intake. It has been proposed that duodenum, jejunum and ileum may respond differently to infused proteins. OBJECTIVE: To investigate differences in ad libitum food intake, feelings of hunger and satiety and the systemic levels of cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), peptide YY (PYY), glucose and insulin after intraduodenal, intrajejunal and intraileal protein infusion. METHODS: Fourteen subjects (four male, mean age: 23±2.1 years, mean body mass index: 21.6±1.8 kg m-2) were intubated with a naso-ileal catheter in this double-blind, randomized, placebo-controlled crossover study. Test days (four in total, executed on consecutive days) started with the ingestion of a standardized breakfast, followed by the infusion of 15 g of protein in the duodenum, jejunum or ileum over a period of 60 min. Food intake was measured by offering an ad libitum meal and Visual Analogue Scale (VAS) scores were used to assess feelings of hunger and satiety. Blood samples were drawn at regular intervals for CCK, GLP-1, PYY, glucose and insulin analyses. RESULTS: Intraileal protein infusion decreased ad libitum food intake compared with both intraduodenal and placebo infusion (ileum: 628.5±63 kcal vs duodenum: 733.6±50 kcal, P<0.01 and placebo: 712.2±53 kcal, P<0.05). GLP-1 concentrations were increased after ileal infusion compared with jejunal and placebo infusion, whereas CCK concentrations were only increased after intraileal protein infusion compared with placebo. None of the treatments affected VAS scores for hunger and satiety nor plasma concentrations of PYY and glucose. CONCLUSIONS: Protein infusion into the ileum decreases food intake during the next meal compared with intraduodenal infusion, whereas it increases systemic levels of GLP-1 compared with protein infusion into the jejunum and placebo respectively.

Ileal brake activation: macronutrient-specific effects on eating behavior?

BACKGROUND: Activation of the ileal brake, by infusing lipid directly into the distal part of the small intestine, alters gastrointestinal (GI) motility and inhibits food intake. The ileal brake effect on eating behavior of the other macronutrients is currently unknown. OBJECTIVE: The objective of this study was to investigate the effects of ileal infusion of sucrose and casein on food intake, release of GI peptides, gastric emptying rate and small-bowel transit time with safflower oil as positive control. DESIGN: This randomized, single-blind, crossover study was performed in 13 healthy subjects (6 male; mean age 26.4±2.9 years; mean body mass index 22.8±0.4 kg m(-2)) who were intubated with a naso-ileal catheter. Thirty minutes after the intake of a standardized breakfast, participants received an ileal infusion, containing control ((C) saline), safflower oil ((HL) 51.7 kcal), low-dose casein ((LP) 17.2 kcal) or high-dose casein ((HP) 51.7 kcal), low-dose sucrose ((LC) 17.2 kcal) and high-dose sucrose ((HC) 51.7 kcal), over a period of 90 min. Food intake was determined during an ad libitum meal. Visual analogue score questionnaires for hunger and satiety and blood samples were collected at regular intervals. RESULTS: Ileal infusion of lipid, protein and carbohydrate resulted in a significant reduction in food intake compared with control (HL: 464.3±90.7 kcal, P<0.001; HP: 458.0±78.6 kcal, P<0.005; HC: 399.0±57.0 kcal, P<0.0001 vs control: 586.7±70.2 kcal, P<0.001, respectively). A reduction in energy intake was still apparent when the caloric amount of infused nutrients was added to the amount eaten during the ad libitum meal.Secretion of cholecystokinin and peptide YY but not of glucagon-like peptide-1 (7-36) was increased during ileal perfusion of fat, carbohydrates and protein. During ileal perfusion of all macronutrients, a delay in gastric emptying and intestinal transit was observed, but differences were not significant compared with control. CONCLUSION: Apart from lipids, also sucrose and casein reduce food intake on ileal infusion, thereby activating the ileal brake. In addition to food intake, also satiety and GI peptide secretion were affected.

Heat-transfer-based detection of L-nicotine, histamine, and serotonin using molecularly imprinted polymers as biomimetic receptors.

In this work, we will present a novel approach for the detection of small molecules with molecularly imprinted polymer (MIP)-type receptors. This heat-transfer method (HTM) is based on the change in heat-transfer resistance imposed upon binding of target molecules to the MIP nanocavities. Simultaneously with that technique, the impedance is measured to validate the results. For proof-of-principle purposes, aluminum electrodes are functionalized with MIP particles, and L-nicotine measurements are performed in phosphate-buffered saline solutions. To determine if this could be extended to other templates, histamine and serotonin samples in buffer solutions are also studied. The developed sensor platform is proven to be specific for a variety of target molecules, which is in agreement with impedance spectroscopy reference tests. In addition, detection limits in the nanomolar range could be achieved, which is well within the physiologically relevant concentration regime. These limits are comparable to impedance spectroscopy, which is considered one of the state-of-the-art techniques for the analysis of small molecules with MIPs. As a first demonstration of the applicability in biological samples, measurements are performed on saliva samples spiked with L-nicotine. In summary, the combination of MIPs with HTM as a novel readout technique enables fast and low-cost measurements in buffer solutions with the possibility of extending to biological samples.

Time of ingestion relative to meal intake determines gastrointestinal responses to a plant sterol-containing yoghurt drink.

PURPOSE: Plant sterol (PS)-enriched food products are known to reduce plasma cholesterol concentrations by inhibiting the absorption of dietary and biliary cholesterol. The physiological responses induced by food intake in the gastrointestinal tract are all important factors in determining the overall effect of PS. The aim of this study was therefore to assess the effect of timing of consumption of a plant sterol (PS)-containing yoghurt drink relative to meal ingestion on gastric emptying (GE) of the drink and gallbladder (GB) volume. METHODS: This is a randomized, single-centre, controlled study with crossover design in 12 healthy male volunteers. Three treatments were tested; a 100 mL PS yoghurt drink (labeled with 1,000 mg acetaminophen) was consumed 45 min prior to, during and 45 min after a solid meal. Plasma samples were taken, and gallbladder volumes were measured at baseline and at regular intervals during a 6-h study period. RESULTS: When consumed before the consumption of a meal, the yoghurt drink exhibited fast GE. The solid meal intake caused a significant contraction of the gallbladder. Consumption of the PS drink before the meal had no significant effect on GB volume as compared to baseline and compared to during and after meal consumption. CONCLUSIONS: The PS-containing drink, which empties fast from the stomach, does not sufficiently trigger gallbladder contraction without co-ingestion of a solid meal and in consequence does not induce the necessary physiological changes needed to allow PS to exhibit their effect on inhibiting cholesterol absorption.

Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, characterized by recurrent abdominal pain or discomfort in combination with disturbed bowel habits in the absence of identifiable organic cause. Visceral hypersensitivity has emerged as a key hypothesis in explaining the painful symptoms in IBS and has been proposed as a "biological hallmark" for the condition. Current techniques of assessing visceral perception include the computerized barostat using rectal distensions, registering responses induced by sensory stimuli including the flexor reflex and cerebral evoked potentials, as well as brain imaging modalities such as functional magnetic resonance imaging and positron emission tomography. These methods have provided further insight into alterations in pain processing in IBS, although the most optimal method and condition remain to be established. In an attempt to give an overview of these methods, a literature search in the electronic databases PubMed and MEDLINE was executed using the search terms "assessment of visceral pain/visceral nociception/visceral hypersensitivity" and "irritable bowel syndrome." Both original articles and review articles were considered for data extraction. This review aims to discuss currently used modalities in assessing visceral perception, along with advantages and limitations, and aims also to define future directions for methodological aspects in visceral pain research. Although novel paradigms such as brain imaging and neurophysiological recordings have been introduced in the study of visceral pain, confirmative studies are warranted to establish their robustness and clinical relevance. Therefore, subjective verbal reporting following rectal distension currently remains the best-validated technique in assessing visceral perception in IBS.

The Effect of a Citrus and Pomegranate Complex on Physical Fitness and Mental Well-Being in Healthy Elderly: A Randomized Placebo-Controlled Trial.

OBJECTIVES: This study investigates whether a citrus and pomegranate complex (CPC) improves physical fitness, mental well-being, and blood biomarkers for oxidative stress and endothelial function in healthy elderly. DESIGN: A randomized placebo-controlled cross-over trial. PARTICIPANTS: The study included 36 healthy elderly aged 60-75 years old. INTERVENTION AND MEASUREMENTS: Participants received four weeks of CPC supplementation and performed the handgrip strength and senior fitness test. Quality of life (QOL) was assessed and blood samples were analyzed for oxidative stress and endothelial function markers. RESULTS: After four weeks of CPC supplementation, handgrip strength significantly improved (p=0.019), compared to placebo. Moreover, the thinking, memory, learning, and concentration facets were improved (p=0.042), compared to placebo, and plasma malondialdehyde decreased, compared to placebo (p=0.033). The intervention did not affect senior fitness and the other QOL domains and blood parameters. CONCLUSION: Four weeks of daily CPC supplementation significantly improves handgrip strength and self-evaluated measures of psychological function in healthy older adults. Further research should focus on mechanisms associated with physical performance.

Effects of Supplementation of the Synbiotic Ecologic® 825/FOS P6 on Intestinal Barrier Function in Healthy Humans: A Randomized Controlled Trial.

BACKGROUND AND AIMS: Probiotics, prebiotics and synbiotics have been suggested as dietary strategies to improve intestinal barrier function. This study aimed to assess the effect of two weeks synbiotic supplementation on intestinal permeability under basal and stressed conditions. Secondary aims were the assessment of two weeks synbiotic supplementation on systemic immune function and gastrointestinal symptoms including defecation pattern. DESIGN: Twenty healthy adults completed a double-blind, controlled, randomized, parallel design study. INTERVENTION: Groups either received synbiotic (1.5 × 1010 CFU Ecologic® 825 + 10 g fructo-oligosaccharides (FOS P6) per day) or control supplements for two weeks. OUTCOMES: Intestinal segment specific permeability was assessed non-invasively by oral administration of multiple sugar probes and, subsequently, assessing the excretion of these probes in urine. This test was conducted at baseline and at the end of intervention, in the absence and in the presence of an indomethacin challenge. Indomethacin was applied to induce a compromised gut state. Plasma zonulin, cytokines and chemokines were measured at baseline and at the end of intervention. Gastrointestinal symptoms and stool frequency were recorded at baseline and daily during intervention. RESULTS: Significantly more male subjects were in the synbiotic group compared to the control group (P = 0.025). Indomethacin significantly increased urinary lactulose/rhamnose ratio versus without indomethacin, both in the control group (P = 0.005) and in the synbiotic group (P = 0.017). Urinary sugar recoveries and ratios, plasma levels of zonulin, cytokines and chemokines, and gastrointestinal symptom scores were not significantly different after control or synbiotic intervention. Stool frequency within the synbiotic group was significantly increased during synbiotic intervention compared to baseline (P = 0.039) and higher compared to control intervention (P = 0.045). CONCLUSION: Two weeks Ecologic® 825/FOS P6 supplementation increased stool frequency, but did not affect intestinal permeability neither under basal nor under indomethacin-induced stressed conditions, immune function or gastrointestinal symptoms in healthy adults.

Paracetamol as a Post Prandial Marker for Gastric Emptying, A Food-Drug Interaction on Absorption.

UNLABELLED: The use of paracetamol as tool to determine gastric emptying was evaluated in a cross over study. Twelve healthy volunteers were included and each of them consumed two low and two high caloric meals. Paracetamol was mixed with a liquid meal and administered by a nasogastric feeding tube. The post prandial paracetamol plasma concentration time curve in all participants and the paracetamol concentration in the stomach content in six participants were determined. It was found that after paracetamol has left the stomach, based on analysis of the stomach content, there was still a substantial rise in the plasma paracetamol concentration time curve. Moreover, the difference in gastric emptying between high and low caloric meals was missed using the plasma paracetamol concentration time curve. The latter curves indicate that (i) part of the paracetamol may leave the stomach much quicker than the meal and (ii) part of the paracetamol may be relatively slowly absorbed in the duodenum. This can be explained by the partition of the homogenous paracetamol-meal mixture in the stomach in an aqueous phase and a solid bolus. The aqueous phase leaves the stomach quickly and the paracetamol in this phase is quickly absorbed in the duodenum, giving rise to the relatively steep increase of the paracetamol concentration in the plasma. The bolus leaves the stomach relatively slowly, and encapsulation by the bolus results in relatively slow uptake of paracetamol from the bolus in the duodenum. These findings implicate that paracetamol is not an accurate post prandial marker for gastric emptying. The paracetamol concentration time curve rather illustrates the food-drug interaction on absorption, which is not only governed by gastric emptying. TRIAL REGISTRATION: ClinicalTrials.gov NCT01335503 Nederlands Trial Register NTR2780.

Randomised clinical study: Aspergillus niger-derived enzyme digests gluten in the stomach of healthy volunteers.

BACKGROUND: Aspergillus niger prolyl endoprotease (AN-PEP) efficiently degrades gluten molecules into non-immunogenic peptides in vitro. AIM: To assess the efficacy of AN-PEP on gluten degradation in a low and high calorie meal in healthy subjects. METHODS: In this randomised, double-blind, placebo-controlled, cross-over study 12 healthy volunteers attended to four test days. A liquid low or high calorie meal (4 g gluten) with AN-PEP or placebo was administered into the stomach. Via a triple-lumen catheter gastric and duodenal aspirates were sampled, and polyethylene glycol (PEG)-3350 was continuously infused. Acetaminophen in the meals tracked gastric emptying time. Gastric and duodenal samples were used to calculate 240-min area under the curve (AUC0-240 min ) of ?-gliadin concentrations. Absolute ?-gliadin AUC0-240 min was calculated using duodenal PEG-3350 concentrations. RESULTS: AN-PEP lowered α-gliadin concentration AUC0-240 min, compared to placebo, from low and high calorie meals in stomach (low: 35 vs. 389 µg × min/mL; high: 53 vs. 386 µg × min/mL; P < 0.001) and duodenum (low: 7 vs. 168 µg × min/mL; high: 4 vs. 32 µg × min/mL; P < 0.001) and absolute α-gliadin AUC0-240 min in the duodenum from low (2813 vs. 31 952 µg × min; P < 0.001) and high (2553 vs. 13 095 µg × min; P = 0.013) calorie meals. In the placebo group, the high compared to low calorie meal slowed gastric emptying and lowered the duodenal α-gliadin concentration AUC0-240 min (32 vs. 168 µg × min/mL; P = 0.001). CONCLUSIONS: AN-PEP significantly enhanced gluten digestion in the stomach of healthy volunteers. Increasing caloric density prolonged gastric residence time of the meal. Since AN-PEP already degraded most gluten from low calorie meals, no incremental effect was observed by increasing meal caloric density. ClinicalTrials.gov, Number: NCT01335503; www.trialregister.nl, Number: NTR2780.

Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study.

BACKGROUND: Altered serotonergic (5-HT) metabolism and visceral perception have been associated with the pathogenesis of irritable bowel syndrome (IBS). Aim of this preliminary study was to assess the effect of the direct precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on systemic 5-HT metabolites and visceral perception and to assess potential differential responses between IBS and controls. METHODS: 15 IBS patients and 15 healthy volunteers participated in this randomized double-blind placebo controlled study. Visceroperception was measured by rectal barostat. The 100 mg 5-HTP or placebo was ingested orally. Serotonergic metabolites were assessed in platelet poor plasma. KEY RESULTS: 5-HTP induces rectal allodynia in a significant number of healthy controls; IBS patients exhibit lowered pain thresholds in both placebo and 5-HTP conditions. 5-HTP induces rectal hyperalgesia in hypersensitive but not in non-hypersensitive IBS patients. Administration of 5-HTP significantly increased plasma 5-HTP levels (p < 0.001), did not affect 5-HT levels (p > 0.05), while levels of the main metabolite of 5-HT, 5-hydroxyindoleacetic acid, increased significantly (p < 0.05) in both groups. The magnitude of these changes observed in 5-HT metabolites was significantly greater in IBS patients. CONCLUSIONS & INFERENCES: Oral administration of 5-HTP induced significant alterations in systemic 5-HT metabolites that were accompanied by increased visceroperception of pain in controls and hypersensitive IBS patients. Changes in 5-HT metabolism appear to be important factors involved in visceral hypersensitivity as the 5-HTP-induced pro-nociceptive response was observed in all hypersensitive IBS patients and to a lesser magnitude in a significant number of healthy controls but in none of the non-hypersensitive IBS patients.

Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers.

OBJECTIVE: To determine whether recombinant human lactoferrin ingestion inhibits nonsteroidal antiinflammatory drugs (NSAID)-induced gastroenteropathy in vivo in healthy volunteers as a model for disorders associated with a rise in permeability of the stomach and the small intestine. DESIGN: A randomized crossover dietary intervention. SUBJECTS AND INTERVENTIONS: In all, 15 healthy volunteers (age 23+/-1.4 y) were tested. A sucrose and a lactulose/rhamnose (L/R) permeability test was performed to assess gastroduodenal and small intestine permeability as indicator of NSAID-induced gastroenteropathy. All subjects consumed standardized meals for 2 days. On the second day at time=-24 h each subject ingested a drink containing 5 g recombinant human lactoferrin or placebo during breakfast. At t=-9 h, subjects ingested the same drink with 75 mg of the NSAID indomethacin and after an overnight fast at t=-1 h subjects consumed the drink and 50 mg indomethacin. After 1 h, at t=0, a permeability test was performed. RESULTS: Small intestine permeability after indomethacin and placebo was significantly higher (L/R ratio=0.036; 0.014-0.092, P<0.05) compared to the permeability observed after ingestion of indomethacin and lactoferrin (0.028; 0.015-0.056), whereas gastroduodenal permeability did not differ between the two interventions (P=0.3). CONCLUSION: Oral recombinant human lactoferrin supplementation during a short-term indomethacin challenge reduced the NSAID-mediated increase in small intestinal permeability and hence may provide a nutritional tool in the treatment of hyperpermeability-associated disorders. SPONSORSHIP: Grant and human recombinant lactoferrin donated from Agennix Inc., Houston, TX.

Serotonergic reinforcement of intestinal barrier function is impaired in irritable bowel syndrome.

BACKGROUND: Alterations in serotonergic (5-HT) metabolism and/or intestinal integrity have been associated with irritable bowel syndrome (IBS). AIMS: To assess the effects of the precursor of 5-HT, 5-hydroxytryptophan (5-HTP), on mucosal 5-HT availability and intestinal integrity, and to assess potential differences between healthy controls and IBS patients. METHODS: Fifteen IBS patients and 15 healthy volunteers participated in this randomised double-blind placebo-controlled study. Intestinal integrity was assessed by dual-sugar test and by determining the mucosal expression of tight junction proteins after ingestion of an oral bolus of 100 mg 5-HTP or placebo. Mucosal serotonergic metabolism was assessed in duodenal biopsy samples. RESULTS: 5-HTP administration significantly increased mucosal levels of 5-HIAA, the main metabolite of 5-HT, in both healthy controls (7.1 ± 1.7 vs. 2.5 ± 0.7 pmol/mg, 5-HTP vs. placebo, P = 0.02) and IBS patients (20.0 ± 4.8 vs. 8.1 ± 1.3 pmol/mg, 5-HTP vs. placebo, P = 0.02), with the latter group showing a significantly larger increase. Lactulose/L-rhamnose ratios were significantly lower after administration of 5-HTP (P < 0.05) in healthy controls and were accompanied by redistribution of zonula occludens-1 (ZO-1), pointing to reinforcement of the barrier. In IBS, expression of the tight junction proteins was significantly lower compared to healthy controls, and 5-HTP resulted in a further decrease in occludin expression. CONCLUSIONS: Oral 5-HTP induced alterations in mucosal 5-HT metabolism. In healthy controls, a reinforcement of the intestinal barrier was seen whereas such reaction was absent in IBS patients. This could indicate the presence of a serotonin-mediated mechanism aimed to reinforce intestinal barrier function, which seems to dysfunction in IBS patients.

Alterations in mucosal neuropeptides in patients with irritable bowel syndrome and ulcerative colitis in remission: a role in pain symptom generation?

BACKGROUND: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder characterized by chronic abdominal pain. The transient receptor potential vanilloid 1 (TRPV1) channel, which is involved in visceral pain signalling, has been shown to be up-regulated in IBS. Activation of TRPV1 leads to the release of neuropeptides, such as somatostatin and substance P (SP). We hypothesized that increased pain perception in IBS could be explained by increased transcription in TRPV1 and/or altered levels of neuropeptides. We therefore assessed the transcription of TRPV1 and the mucosal concentration of somatostatin and SP in IBS in comparison to healthy volunteers and patients with ulcerative colitis (UC) in remission as disease controls, and to ascertain their relationship to pain symptoms. METHOD: Sigmoid colonic mucosal samples were collected from 12 patients with IBS, 34 patients with UC in remission and 9 healthy volunteers, in which groups TRPV1 mRNA levels were determined using quantitative polymerase chain reaction and neuropeptide concentrations by radioimmunoassay. Pain symptom intensity was determined by questionnaires. RESULTS: Transcription of TRPV1 as well as the concentration of neuropeptides were significantly higher in IBS, but only the former correlated with pain symptom severity. CONCLUSION: Increased transcription of TRPV1 may provide a possible explanation for pain generation in IBS. While the neuropeptides SP and somatostatin were both found to be increased in IBS, these changes are not sufficient to explain pain generation. Pain generation in IBS is probably explained by a complex redundancy in the regulation of local nociceptive mechanisms, which remains a subject of intensive investigation.

Revisiting concepts of visceral nociception in irritable bowel syndrome.

BACKGROUND AND OBJECTIVE: Irritable bowel syndrome (IBS) is a common disorder characterized by abdominal pain related to defecation with a change in bowel habit. Patients with IBS often exhibit increased visceral sensitivity, which can be tested clinically by rectal balloon distension procedures. This paper aims to give an overview of mechanisms involved in visceral hypersensitivity in IBS by reviewing recent literature. DATABASES AND DATA TREATMENT: A literature search in the electronic databases Pubmed and MEDLINE was executed using the search terms 'visceral pain' or 'visceral nociception' or 'visceral hypersensitivity' and 'irritable bowel syndrome.' Both original articles and review articles were considered for data extraction. RESULTS: Recent advances in molecular neurophysiology provide knowledge to better understand the underlying mechanism in pain generation in the human gut, in particular, in IBS patients. Sensitization of peripheral nociceptive afferents, more specifically high-threshold afferents, has been proposed as one of the principle mechanism in the development of visceral hypersensitivity. On the other hand, central mechanisms also play an important role. In terms of clinical testing of visceral perception, considerable discrepancies remain, however, across different centres. CONCLUSION: Alterations in the modulatory balance of pro- and antinociceptive central processing of noxious peripheral input may serve as in integrative hypothesis for explaining visceral hypersensitivity in IBS. Nevertheless, it remains troublesome to estimate the contribution of central and peripheral factors in visceral hypersensitivity, posing a challenge in determining effective therapeutic entities.

Alternative procedure to shorten rectal barostat procedure for the assessment of rectal compliance and visceral perception: a feasibility study.

BACKGROUND: Barostat methodology is widely used for assessing visceral perception. Different barostat protocols are described with respect to the measurement of rectal compliance and visceral perception. The choice of protocols affects the duration, which is normally 60-90 min, and accuracy of the procedure. This study aimed to shorten the procedure by using the semi-random distension protocol for both compliance and visceral perception measurement and a correction based on rectal capacity (RC) instead of minimal distension pressure (MDP). METHODS: Twelve irritable bowel syndrome (IBS) patients (7 females) and 11 healthy controls (8 females) underwent a barostat procedure. Compliance was determined during both a staircase distension and a semi-random protocol. Visceral perception data were compared as a function of pressure or relative volume, corrected for MDP or RC, respectively. RESULTS: Compliance measurement using the semi-random protocol instead of the staircase distension protocol resulted in an overestimation in healthy volunteers, but not in IBS patients. The overall conclusion that IBS patients had a lower compliance compared to controls was not different between protocols. Data presentation of the visceral perception scores as a function of corrected volume instead of pressures corrected for MDP did not alter the conclusion that sensation scores in IBS patients were higher as compared to healthy controls. CONCLUSIONS: This study showed that barostat procedures may be shortened by approximately 20 min, without losing the ability to discriminate between healthy controls and IBS patients. A correction for RC instead of MDP may improve the accuracy of the procedure.

Gastrointestinal targets to modulate satiety and food intake.

This review discusses the role of enteroendocrine cells in the gastrointestinal tract as chemoreceptors that sense intraluminal contents and induce changes in food intake through the release of signalling substances, such as satiety hormones. Recent evidence supports the concept that chemosensing in the gut involves G protein-coupled receptors (GPCRs) that are known to mediate gustatory signals in the oral cavity. GPCRs can be grouped into several families, depending on the stimuli to which they respond, e.g. proteins, amino acids, carbohydrates, fatty acids, or tastants. Sensing of these stimuli by GPCRs results in hormone secretions of enteroendocrine cells, which participate in the control of food intake. A better understanding of the stimuli that induce the strongest binding with these receptors, and thus induce a strong release of hormones, can be a very useful strategy for the development of novel foods in the treatment of obesity.

Peptide-YY is released by the intestinal cell line STC-1.

Dietary modulation of the response of gut satiety hormones, which partly regulate food intake, provides a promising treatment for overweight and obesity. Gut-derived cell lines such as STC-1 are widely used to investigate these hormonal responses to nutrients. To date, no peptide-YY (PYY) secreting cell line has been identified. The aim of this study was to investigate whether STC-1 cells are able to secrete PYY and if so, whether dietary compounds can modulate PYY secretion. The effects of fatty acid types C4:0, C12:0, C14:0, C16:0, and C18:0 on PYY release were investigated by measuring PYY in the supernatant after 30, 60, 90, and 120 min of incubation, respectively, using RIA assays. The STC-1 cells were able to secrete PYY in a time-dependent manner. It was shown that after 30 min, C4:0, C12:0, C16:0, and C18:0 caused increased PYY levels compared to the control. At time points 60 and 90 min, C4:0 and C18:0 induced elevated PYY levels compared to the control. After 120 min, C4:0, C14:0, and C18:0 caused elevated levels compared to the control. We are the first to show that the STC-1 cells are also able to secrete PYY next to cholecystokinin (CCK) and glucagon-like peptide 1 (GLP-1). Addition of fatty acids resulted in increased levels of PYY, which is consistent with the literature describing human studies. We conclude that the STC-1 cell line provides an appropriate cell line for screening the effects of ingredients on the release of the satiety-related gut hormones CCK, GLP-1, and PYY.

Understanding the role of tryptophan and serotonin metabolism in gastrointestinal function.

Tryptophan is the precursor of a wide array of metabolites, which are involved in a variety of aspects of human nutrition and metabolism. Accumulating evidence suggests a role of tryptophan metabolites, especially serotonin (5-hydroxytryptamin) in intestinal (patho) physiology, although mechanisms of action are still poorly understood. Alterations of serotonin metabolism may give rise to gastrointestinal dysfunction. Recently, it has been postulated that other metabolites of tryptophan, mostly of the kynurenine pathway, also play a role in regulating gut function. This review analyses the current knowledge of the interrelationship between tryptophan metabolic pathways and summarizes the existing scientific evidence regarding the role of tryptophan metabolites in intestinal function and in the pathogenesis of gastrointestinal diseases.