The endocrine effects of bitter tastant administration in the gastrointestinal system: intragastric versus intraduodenal administration.

Bitter tastants are recently introduced as potential hunger-suppressive compounds, the so-called "Bitter pill." However, the literature about bitter administration lacks consistency in methods and findings. We want to test whether hunger ratings and hormone plasma levels are affected by: ) the site of administration: intragastrically (IG) or intraduodenally (ID), ) the bitter tastant itself, quinine hydrochloride (QHCl) or denatonium benzoate (DB), and ) the timing of infusion.

High-resolution manometry reveals different effect of polyethylene glycol, bisacodyl, and prucalopride on colonic motility in healthy subjects: An acute, open label, randomized, crossover, reader-blinded study with potential clinical implications.

Background: Polyethylene glycol (PEG), bisacodyl, and prucalopride have been reported to be more effective than placebo in treating patients with constipation but about 50% of the patients still do not respond to these medications. Only bisacodyl and prucalopride are expected to directly stimulate the colonic motility in humans in vivo. As no previous study has done this, the aim of the study was to investigate the effect of PEG, bisacodyl, and prucalopride as compared to placebo on colonic motility assessed by means of the high-resolution manometry (HRM) in healthy subjects.

Manometric demonstration of duodenal/jejunal motor function consistent with the duodenal brake mechanism.

Background: High-resolution manometric studies below the stomach are rare due to technical limitations of traditional manometry catheters. Consequently, specific motor patterns and their impact on gastric and small bowel function are not well understood. High-resolution manometry was used to record fed-state motor patterns in the antro-jejunal segment and relate these to fasting motor function.

Exploring the impact of real-life dosing conditions on intraluminal and systemic concentrations of atazanavir in parallel with gastric motility recording in healthy subjects.

This work strived to explore gastrointestinal (GI) dissolution, supersaturation and precipitation of the weakly basic drug atazanavir in humans under different 'real-life' intake conditions. The impact of GI pH and motility on these processes was thoroughly explored. In a cross-over study, atazanavir (Reyataz®) was orally administered to 5 healthy subjects with (i) a glass of water, (ii) a glass of Coca-Cola® and (iii) a glass of water under hypochlorhydric conditions (induced by concomitant intake of a proton-pump inhibitor (PPI)).

Acute administration of fructans increases the number of transient lower esophageal sphincter relaxations in healthy volunteers.

Introduction: Dietary measures are often advised to patients with gastro-esophageal reflux disease (GERD). Fermentable Oligo-, Di-, Mono-saccharides and Polyols (FODMAPs) induce lower gastrointestinal (GI) symptoms. However, their effects on esophageal motility, including transient lower esophageal sphincter relaxations (TLESRs), reflux events and GERD symptoms are unknown.

Randomised clinical trial: the DPP-4 inhibitor, vildagliptin, inhibits gastric accommodation and increases glucagon-like peptide-1 plasma levels in healthy volunteers.

Background: Dipeptidyl peptidase-4 (DPP-4) inactivates glucagon-like peptide-1 (GLP-1). Whether DPP-4 inhibition affects GLP-1 metabolism and/or food intake in humans remains unknown.

Aims: To evaluate the effect of vildagliptin (DPP-4 inhibitor) on gastric accommodation and ad libitum food intake in healthy volunteers (HVs) METHODS: The effects of acute oral vildagliptin administration (50 mg) were evaluated in two randomised, placebo-controlled, single-blinded trials.

Motilin: from gastric motility stimulation to hunger signalling.

After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution - with the use of knockout models - sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease.

Obesity alters adrenergic and chemosensory signaling pathways that regulate ghrelin secretion in the human gut.

Chemosensory signaling in organs such as the mouth and gut contributes to the mechanisms that control metabolism. We investigated the chemosensory pathways that regulate secretion of the hunger hormone ghrelin in response to neurotransmitters, bitter and sweet tastants at the cellular level in the human gut mucosa, and the disturbances in this regulatory pathway induced by obesity. Obesity impaired ghrelin protein production and adrenalin-induced ghrelin secretion in fundic cells, which was counterbalanced by somatostatin.

The optimal order of stimulation modalities and reproducibility of the multimodal esophageal stimulation paradigm.

Background: Esophageal hypersensitivity can be triggered by different stimuli. We use a multimodal stimulation model to study esophageal sensitivity to four sensory modalities: thermal, mechanical, electrical, and chemical stimulation. The optimal order of these stimulations needs further validation.

Effects of caloric and noncaloric sweeteners on antroduodenal motility, gastrointestinal hormone secretion and appetite-related sensations in healthy subjects.

Background: Activation of gastrointestinal (GI) sweet taste receptors by caloric sweeteners triggers secretion of anorexigenic and inhibition of orexigenic GI hormones to regulate food intake. The effect of noncaloric sweeteners on these mechanisms is controversial. We have recently shown that motilin-induced gastric phase III contractions signal hunger feelings, thereby identifying GI motility, and its regulatory hormone motilin, as novel players in food intake regulation.

Effect of motilin receptor activation on food intake and food timing.

Background: Motilin plasma concentrations are positively correlated with hunger ratings during the fasting state. Moreover, the motilin agonist erythromycin stimulates meal requests.

Objectives: The first aim of the study was to evaluate the effect of erythromycin on ad libitum food intake.

Intragastric quinine administration decreases hedonic eating in healthy women through peptide-mediated gut-brain signaling mechanisms.

Intragastric bitter tastants may decrease appetite and food intake. We aimed to investigate the gut-brain signaling and brain mechanisms underlying these effects. Brain responses to intragastric quinine-hydrochloride (QHCl, 10 µmol/kg) or placebo infusion were recorded using functional magnetic resonance imaging in 15 healthy women.

The effect of arabinoxylooligosaccharides on upper gastroduodenal motility and hunger ratings in humans.

Background And Aims: Prebiotics such as Arabinoxylooligosaccharides (AXOS) are non-digestible, fermentable food ingredients stimulating growth/activity of colonic bacteria with enhanced carbohydrates fermentation (CF) in humans. The migrating motor complex (MMC) of the gastrointestinal tract has been recently identified as an important hunger signal, but no data are available yet on the role of acute CF on MMC activity and related hunger ratings. Thus, we aimed to study the effect of acute AXOS CF on MMC and hunger in humans.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially.

Manometric evaluation of the motilin receptor agonist camicinal (GSK962040) in humans.

Background: The gut hormone motilin stimulates gastrointestinal motility by inducing gastric phase III of the migrating motor complex (MMC) and enhancing the rate of gastric emptying. Camicinal (GSK962040), a small molecule motilin receptor agonist, has been shown to increase gastrointestinal motility.

Methods: In this proof of concept study the effects of camicinal on MMC activity, esophageal and gastric pH was evaluated in eight healthy volunteers as a secondary endpoint.

Intragastric infusion of the bitter tastant quinine suppresses hormone release and antral motility during the fasting state in healthy female volunteers.

Background: Intragastric administration of the bitter tastant denatonium benzoate inhibits the increase of motilin plasma levels and antral contractility. While these findings suggest that gastrointestinal bitter taste receptors could be new targets to modulate gastrointestinal motility and hormone release, they need confirmation with other bitter receptor agonists. The primary aim was to evaluate the effect of intragastric administration of the bitter tastant quinine-hydrochloride (QHCl) on motilin and ghrelin plasma levels.

The Effect of Sparkling Water on Intraluminal Formulation Behavior and Systemic Drug Performance.

In the context of mediating intra- and interindividual variability in systemic drug exposure after oral drug administration, this small-scale, crossover study aimed to investigate the effect of drug intake with sparkling water on fasted state gastric motor function and subsequent (variability in) intraluminal and systemic drug disposition. For this purpose, healthy human volunteers were asked to ingest a conventional paracetamol tablet with either tap or sparkling water, after which antroduodenal motility and intraluminal and systemic drug disposition were monitored as a function of time. Ingestion of sparkling water led to the occurrence of transient pressure events in the upper gastrointestinal tract for all volunteers, although the duration and frequency of the observed effect were subject to variability.

Intragastric infusion of denatonium benzoate attenuates interdigestive gastric motility and hunger scores in healthy female volunteers.

Denatonium benzoate (DB) has been shown to influence ongoing ingestive behavior and gut peptide secretion. We studied how the intragastric administration of DB affects interdigestive motility, motilin and ghrelin plasma concentrations, hunger and satiety ratings, and food intake in healthy volunteers. Lingual bitter taste sensitivity was tested with the use of 6 concentrations of DB in 65 subjects.

Pan-Colonic Pressurizations Associated With Relaxation of the Anal Sphincter in Health and Disease: A New Colonic Motor Pattern Identified Using High-Resolution Manometry.

Objectives: Only a few studies have applied high-resolution manometry (HRM) to the study of colonic motility in adults and none of them have concurrently evaluated colonic and anal motor activity. The aim of the study was to evaluate colonic and anal motor activity by means of HRM in healthy subjects. As the present study revealed the presence of a new colonic motor pattern (pan-colonic pressurizations) in healthy subjects, three additional studies were conducted: the first and the second to exclude that this motor event results from an artifact due to abdominal wall contraction and to confirm its modulation by cholinergic stimulation, and the third, as pilot study, to test the hypothesis that this colonic pattern is defective in patients with chronic constipation refractory to current pharmacological treatments.

The effect of arabinoxylooligosaccharides on gastric sensory-motor function and nutrient tolerance in man.

Background: Intestinal microbiota regulates gastrointestinal sensory-motor function. Prebiotics such as arabinoxylan-oligosaccharide (AXOS) are non-digestible, fermentable food ingredients beneficially affecting intestinal microbiota, colon activity, and improving human health. We wanted to investigate whether acute AXOS or maltodextrin (placebo) administration may alter gastric sensitivity (GS), accommodation (GA), nutrient tolerance (NT) in man.

The motilin receptor agonist erythromycin stimulates hunger and food intake through a cholinergic pathway.

Background: Motilin-induced phase III contractions have been identified as a hunger signal. These phase III contractions occur as part of the migrating motor complex (MMC), a contractility pattern of the gastrointestinal tract during fasting. The mechanism involved in this association between subjective hunger feelings and gastrointestinal motility during the MMC is largely unknown, however, as is its ability to stimulate food intake.

Redefining the functional roles of the gastrointestinal migrating motor complex and motilin in small bacterial overgrowth and hunger signaling.

During the fasting state the upper gastrointestinal tract exhibits a specific periodic migrating contraction pattern that is known as the migrating motor complex (MMC). Three different phases can be distinguished during the MMC. Phase III of the MMC is the most active of the three and can start either in the stomach or small intestine.

Higher plasma motilin levels in obese patients decrease after Roux-en-Y gastric bypass surgery and regulate hunger.

Objective: Motilin-induced phase III contractions of the migrating motor complex (MMC) signal hunger in healthy volunteers. The current aim was to study the role of motilin as a hunger-inducing factor in obese patients and to evaluate the effect of Roux-en-Y gastric bypass (RYGB) surgery on plasma motilin levels and hunger scores.

Design: Motilin and ghrelin plasma levels were determined during a complete MMC cycle in controls and obese patients selected for RYGB before, 6 months and 1 year after surgery.