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This laboratory practical requires first-year students to anticipate the effects of drugs active at cholinergic and adrenergic receptors on gut motility in order to design experiments during an authentic inquiry exercise. Rather than specifying a strict sequence of drug additions that aim to provide ideal demonstrations of pharmacological and physiological antagonism, I have instead designed switches into the drugs provided and set students, working in small teams, the task of identifying the switched drugs, an inquiry activity. To extend the teamwork aspect, laboratory reports were submitted by the student teams rather than individual students. Staff observed that discussions within the teams were stimulated by the inquiry-led nature of the practical. The quality of the laboratory reports submitted by teams were substantially improved over the individual reports submitted in previous years. (Students previously worked in teams, but simply followed a list of prescribed experiments and wrote individual reports.) Although, in conversation, teams of students had an improved understanding of the regulation of gut motility by the parasympathetic and sympathetic divisions of the autonomic nervous system and could readily distinguish between pharmacological and functional antagonism, no attempt was made to evaluate learning because the revision was triggered by the observed effect of a technical error and was not otherwise planned. It is likely that laboratory practicals, in general, would benefit from inclusion of inquiry.

Background In recent years, high-resolution manometry has been used in an attempt to gain a greater insight into the physiology/pathophysiology of colonic contractile activity in healthy adults and patients with colonic motility disorders. New colonic motor patterns have been identified and characterized, however, the clinical significance of these findings remains undetermined. Purpose This review will assess the current literature on colonic high-resolution manometry and determine if this procedure has advanced our understanding of colonic motility. The limitations, future directions, and the potential of this technique to assess the effects of treatment upon colonic motor patterns will also be discussed.

Although critical for studies of gut motility and intestinal regeneration, the in vitro culture of intestinal muscularis with peristaltic function remains a significant challenge. Periodic contractions of intestinal muscularis result from the coordinated activity of smooth muscle cells (SMC), the enteric nervous system (ENS), and interstitial cells of Cajal (ICC). Reproducing this activity requires the preservation of all these cells in one system. Here we report the first serum-free culture methodology that consistently maintains spontaneous and periodic contractions of murine and human intestinal muscularis cells for months. In this system, SMC expressed the mature marker myosin heavy chain, and multipolar/dipolar ICC, uniaxonal/multipolar neurons and glial cells were present. Furthermore, drugs affecting ENS, ICC or SMC altered the contractions. Combining this method with scaffolds, contracting cell sheets were formed with organized architecture. With the addition of intestinal epithelial cells, this platform enabled at least 9 types of cells from mucosa and muscularis to coexist and function. The method constitutes a powerful tool for mechanistic studies of gut motility disorders and the regeneration of full-thickness engineered intestine.In the small intestine, the mucosa processes partially digested food and absorbs nutrients while the muscularis actuates the peristaltic flow to transport luminal content aborally. Gut motility is central to its digestive and absorptive function. The intestinal muscularis contains various types of cells: of these, smooth muscle cells, the enteric nervous system (ENS)1,2, and the pacemaker interstitial cells of Cajal (ICC)3 are three important players involved in the development of gut motility. Recent studies on intestinal tissue engineering have highlighted the importance of regenerating the functional intestinal muscularis4–9. A variety of systems derived from different cell sources, including pluripotent stem cells (PSC)4–6, embryonic stem cells (ESC)7 and primary tissue8,9, have been established to accomplish this goal and different contractile activities were developed in these systems. Notably, spontaneous contractions have been generated in culture systems that contained both ICC and smooth muscle cells4,6,10–13. In addition, electrical-induced neurogenic contractions were also successfully produced4,5,8 when ENS was introduced into culture. In one of the most recent studies, both spontaneous contractions and electrical-induced neurogenic contractions were developed in a PSC-based culture system4.

The goal of this review is to review the current status of prokinetics and to place it in historical context. Impaired motility and thus propulsion have long been thought to play important roles in the pathogenesis of a number of gastrointestinal disorders including gastroesophageal reflux disease (GERD), gastroparesis, chronic idiopathic pseudo-obstruction, and constipation. Historically, disordered motility was also thought to contribute to a number of functional gastrointestinal disorders such as functional dyspepsia (FD) and irritable bowel syndrome (IBS). As we learn more of the pathophysiology of FD, IBS, GERD, constipation, and gastroparesis, the limitations of a therapeutic strategy based on the stimulation of motility (i.e., the use of a prokinetic) have become apparent and the disappointments of the past explained. The development of prokinetic drugs has also been hampered by the non-selective nature of many of the agents studied to date which resulted in some unexpected side effects. There is still an unmet need for an effective and safe prokinetic, but drug development in this area must be mindful of the challenges of the area and the need for selectivity for a given target receptor.

Gastrointestinal motility disorders affect millions of people worldwide, resulting in significant morbidity and mortality. Current treatments for these disorders are inadequate and often provide little to no relief for patients. As a result, gastrointestinal motility disorders produce substantial long-term social and economic burdens in both developed and developing countries. These limited treatment options arise largely from our relatively poor understanding of the molecular etiology for the majority of gastrointestinal motility disorders. In turn, this is due to our limited access to normal or diseased human gut tissue for use in research. In particular while the interstitial cells of Cajal (ICC) are known to be important for gastrointestinal motility, little is known of how these cells function or how they are involved in disease initiation and progression. The advent of human pluripotent stem cell technology offers an opportunity to generate large amounts of human tissue for both research and clinical applications. The application of this technology to gastrointestinal motility disorders is currently only in its infancy and as yet no studies have described ICC production from human pluripotent cells. By considering the present understanding of the anatomical, cellular and molecular basis of gut motility with particular emphasis on ICC, this review provides a clear framework for the application of human pluripotent stem cell technology to answer fundamental questions of ICC involvement in gut motility.

Introduction: Small intestinal bacterial overgrowth syndrome (SIBO) is defined as an increased number of nonpathogenic bacteria over 10 5 organisms in 1 millilitre of small intestine content. The most common predisposing factors include, among others, gut motility disorders and chronic use of proton pump inhibitors. The results of recent studies indicate the importance of SIBO in gastrointestinal diseases. Aim: To assess the prevalence of SIBO in children with abdominal pain. Material and methods: One hundred children (59 girls and 41 boys) aged from 4 to 17 years (mean age: 10.47 ±3.73 years), hospitalised due to abdominal pain, were enrolled in the study. Hydrogen breath test (HBT) with lactulose was established among all patients. Expired air was analysed using a Gastrolyzer (Bedfont). Results: The HBT result was positive in 63 (63%) children with abdominal pain; including 40 girls (67.8%) and 23 boys (56.1%). The test was positive in the group of 29 (46%) children aged under 10 years and in the group of 34 (54%) children aged over 10 years. Among the patients who reported for the control study 88% achieved a normalisation of HBT after treatment. Conclusions: The prevalence of positive HBT results in the group of patients with abdominal pain is over 60%. Small intestinal bacterial overgrowth syndrome should be considered as one of the causes of abdominal pain in children. The SIBO in children shows a good response to treatment.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disorder which represents a major cost to health-care services. The diagnosis of IBS is currently performed by means of symptom-based diagnostic criteria, but there has been an ongoing interest in developing biomarkers which could simplify the diagnosis and/or evaluating the effect of treatments. This article reviews the current literature concerning the proposed biomarkers including those of altered gut motility, of visceral hypersensitivity, of abnormal brain mechanisms, of serum, fecal and mucosal inflammation and of increased intestinal permeability.

Summary StatementWe present a new image analysis technique using image velocimetry and spectral analysis that returns quantitative measures of gut contraction strength, frequency, and wave speed that can be used to study gut motility and other cellular movements.AbstractNormal gut function requires rhythmic and coordinated movements that are affected by developmental processes, physical and chemical stimuli, and many debilitating diseases. The imaging and characterization of gut motility, especially regarding periodic, propagative contractions driving material transport, are therefore critical goals. Whereas previous image analysis approaches have successfully extracted properties related to temporal frequency of motility modes, robust measures of contraction magnitude remain elusive. We developed a new image analysis method based on image velocimetry and spectral analysis that reveals temporal characteristics such as frequency and wave propagation speed, while also providing quantitative measures of the amplitude of gut motions. We validate this approach using several challenges to larval zebrafish, imaged with differential interference contrast microscopy. Both acetylcholine exposure and feeding increase frequency and amplitude of motility. Larvae lacking enteric nervous system gut innervation show the same average motility frequency, but reduced and less variable amplitude compared to wild-types. Our image analysis approach enables insights into gut dynamics in a wide variety of developmental and physiological contexts and can also be extended to analyze other types of cell movements.

BACKGROUND: Gastrointestinal symptoms are common in the general population and may originate from disturbances in gut motility. However, fundamental mechanistic understanding of motility remains inadequate, especially of the less accessible regions of the small bowel and colon. Hence, refinement and validation of objective methods to evaluate motility of the whole gut is important. Such techniques may be applied in clinical settings as diagnostic tools, in research to elucidate underlying mechanisms of diseases, and to evaluate how the gut responds to various drugs. A wide array of such methods exists; however, a limited number are used universally due to drawbacks like radiation exposure, lack of standardization, and difficulties interpreting data. In recent years, several new methods such as the 3D-Transit system and magnetic resonance imaging assessments on small bowel and colonic motility have emerged, with the advantages that they are less invasive, use no radiation, and provide much more detailed information.PURPOSE: This review outlines well-established and emerging methods to evaluate small bowel and colonic motility in clinical settings and in research. The latter include the 3D-Transit system, magnetic resonance imaging assessments, and high-resolution manometry. Procedures, indications, and the relative strengths and weaknesses of each method are summarized.

This review is the first in a series of three articles considering how different types of dietary fibre may affect how the gut functions and gut health. This first review will focus on the impact of dietary fibre intake on the upper gastrointestinal tract (i.e. the mouth, oesophagus and stomach). While a larger body of evidence links fibre intake to bowel health and disease, it is apparent that the presence of fibre, whether as an added ingredient in foods, or as an integral part of the structure of plant foods, also plays key roles on oral and gastric secretions and upper gut motility. These actions are possibly modulated through fibre’s effects on the physicochemical properties of luminal contents in the gut.\ud \ud The major physiological functions of the mouth, oesophagus and stomach are discussed and recent evidence relating dietary fibre intake to these actions is introduced. A summary of evidence linking habitual dietary fibre consumption to major mucosal diseases of the upper gastrointestinal tract is also provided.

The most important reason for functional diarrhea in clinical practice is diarrhea-predominant irritable bowel syndrome (IBS) which is characterized by chronic intermittent diarrhea and abdominal pain. The pathophysiology underlying IBS is complex and includes visceral hypersensitivity, abnormal gut motility and autonomous nervous system dysfunction as well as genetic and psychosocial factors. Treatment should be tailored to the individual's symptoms and involves general measures, pharmacological treatments, dietary interventions, psychotherapy and complementary and alternative approaches. The following manuscript will give an overview over pathophysiology, reasonable investigations and treatment of IBS.

Gastrointestinal manifestations are the commonest internal organ complications of systemic sclerosis and are a major cause of morbidity. The commonest features are gastro-oesophageal reflux and chronic constipation, both reflecting altered gut motility and contractility. However, there are many other manifestations that span the entire gastrointestinal tract.

Dragon fruit oligosaccharide (DFO) has a prebiotic property which improves gut health by selectively stimulating the colonic microbiota. Altering microbiota composition may affect intestinal motility. However, no study has been done to understand the DFO effects on gut motor functions. This research thus aimed to investigate the DFO effects on mice colons compared to the prebiotic fructo-oligosaccharide (FOS) and probiotic bifidobacteria. The mice in this study received distilled water; 100, 500, and 1000 mg/kg DFO; 1000 mg/kg FOS; or 109 CFU Bifidobacterium animalis daily for 1 week and some treatments for 2 weeks. Gastrointestinal transits were analysed and motility patterns, smooth muscle (SM) contractions and morphological structures of the colons were assessed. Administration of FOS, 500 and 1000 mg/kg DFO significantly increased fecal output when compared to the control group. In mice treated with FOS and bifidobacteria, gut transit time was reduced, while upper gut transit was increased in comparison to DFO groups. Spatiotemporal maps of colonic wall motions showed that DFO increased the number of colonic non-propagation contractions and fecal pellet velocity, consistent with the results from groups treated with FOS and bifidobacteria. DFO also increased the amplitude and duration of colonic SM contractions. Histological stains showed normal epithelia, crypts, goblet cells, and SM thickness in all groups. In conclusion, DFO increased colonic SM contractions without morphological change and acted as a bulk-forming and stimulant laxative to increase fecal output and intestinal motility. Thus, DFO as a dietary supplement may promote gut health and correct gastrointestinal motility disorders.

Calcium-activated chloride channels (CaCCs) are critical in regulating neural excitability, nociception, smooth muscle contraction, secretion and gut motility. Besides Ca2 - and voltage-dependent activation, another hallmark of TMEM16A-CaCC is time-dependent desensitization or rundown, the mechanism of which is unclear. Here we report that phosphatidylinositol-(4,5)bisphosphate (PIP2) controls TMEM16A desensitization by stabilizing the channel pore, which is formed by a PIP2 binding ‘regulatory module’ of transmembrane segments (TMs) 3-5 and a ‘Ca2 -binding module’ of TMs6-8. Under sub-micromolar Ca2 , PIP2 dissociation from the ‘regulatory module’ leads to transient pore collapse and desensitization, which can be rapidly reversed by exogenous PIP2, higher Ca2 or voltage. Sustained channel opening under saturating Ca2 requires PIP2 to prevent the persistent pore collapse and desensitization, whose recovery needs prolonged exogenous PIP2 exposure. The PIP2-dependent, bimodal desensitization mechanism and the proposed modular design of TMEM16A pore can shine lights on understanding the structure, function, regulation and physiology of TMEM16 family.

Postoperative patients with Subarachnoid Block anesthesia will experience paralytic ileus. Various efforts to overcome this have been carried out, including early mobilization, chewing gum, warm compresses, and acupuncture. The actions taken have not yet shown maximum results. This study aimed to analyze the effect of ST-36 acupressure on gut motility and flatus time in postoperative patients with Subarachnoid Block anesthesia. This research used Quasi-Experiment with pretest-posttest group design. Population in this research was post operation patient with Subarachnoid Block anesthesia in Sidoarjo Hospital. A sample of 14 respondents in control group and 14 respondents in experimental group were obtained using purposive sampling technique. Data retrieval was done by criteria using lidodex 100mg/2ml anesthetic or 5% lidocain + adrenaline. Data were analyzed using independent t test. The result showed that there was difference average frequency of gut motility between control group and experimental group after given intervention ST-36 acupressure (p=0.013). The time of flatus showed that there were no significant differences in the two groups (p = 0.262). It can be concluded that ST-36 acupressure can increase gut motility, whereas it did not affect flatus time.

Parenteral nutrition (PN) is a necessary therapy used to feed patients with gastrointestinal dysfunction. Unfortunately, PN results in intestinal atrophy and changes to host immune function. PN may also induce additional effects on gut motility that we hypothesized would result from changes in the enteric nervous system.Mice received an intravenous (i.v.) catheter and were randomized to chow (n = 5), i.v. PN (n = 6), or i.v. PN + bombesin (BBS, 15 μg/kg, 3×/d) (n = 6) for 5 d. Colons were removed and dissected to measure the length and circumference. Enteric neuronal density and neurotransmitter expression were determined by co-immunostaining whole-mount tissue with Hu and neuronal nitric oxide synthase (nNOS).The number of myenteric neurons expressing Hu and nNOS increased per unit length in the mid-colon during PN treatment compared with chow. This increase was abrogated by the addition of BBS to the PN regimen. However, the percentage of nNOS-expressing neurons was not significantly altered by PN. Morphometric analysis revealed a decrease in the length and circumference of the colon during PN administration that was partially normalized by supplementation of PN with BBS. A significant reduction in total fecal output was observed in PN animals compared with chow and was increased by mice receiving BBS in addition to PN.PN causes a constriction of the bowel wall, reducing not only the length but also the circumference of the colon. These changes cause a condensation of enteric neurons but no difference in neurotransmitter expression. BBS supplementation partially restores the constriction and increases the fecal output during PN treatment compared with PN treatment alone.

Endurance horses are subjected to heightened stress even after several conditioning protocols. Hence, the goal of this study was to examine the effect of age and performance on the hematology, biochemistry, and physical parameters after an endurance race. Eighteen horses aged 6-15 years were grouped into 80-km race category. All the horses were physically examined, and blood samples were collected postrace. After physical examination, the poor (n = 9) and good (n = 9) performance horses were identified. Potassium concentration was significantly higher (P < .05) in the good performance horses; chloride concentration was significantly higher (P < .05) in the poor performance horses. The mean blood glucose concentration of the poor performance horses in all the age-groups was significantly higher (P < .05). The mean blood lactate concentration was significantly lower (P < .05) in the poor performance horses. There was significant effect of performance on heart rate (P < .031), capillary refill time (P < .013), and gut motility (P < .05). Univariate Fisher exact test results were significantly higher for skin recoil (P < .03), mucous membrane (P < .03), and gait (P < .04) in the performance categories. In conclusion, the influence of age was seen in the poor performance category in relation to lactate, but age did not influence other physical, hematological, and biochemical parameters of the endurance horses. Thus, further studies are required to determine whether physical, hematological, and biochemical parameters during training could be used to estimate performance in endurance horses based on age.

Aim Recently there has been an increased interest in using electrical stimulation to regulate gut motility generally and particularly for the treatment of slow-transit constipation. In this preliminary canine study, we aimed to study the effects of colonic electrical stimulation (CES) on colonic motility and transit. Method Nine dogs, each equipped with a pair of serosal colon electrodes and a proximal colon cannula were randomized to receive: (i) sham-CES, (ii) long pulse CES (20 cpm, 300 ms, 6 mA) or (iii) pulse train CES (40 Hz, 6 ms, 6 mA). Animals underwent assessment of colonic contractions via manometry, and of colonic transit by inserting 24 radiopaque markers via the colonic cannula and radiographically monitoring the markers at 2, 4 and 6 h following their insertion. The colonic transit was assessed by the geometric centre. Results We found that, compared with sham-CES, pulse train CES, but not long pulse CES, significantly increased the overall colonic motility index twofold and accelerated the colonic transit by 104% at 2 h, by 60% at 4 h and by 31% at 6 h (P = 0.01, P = 0.02 and P = 0.03 vs sham-CES at 2, 4 and 6 h, respectively). The accelerating effect of pulse train CES was found to be mediated via both cholinergic and nitrergic pathways. Conclusion CES with pulse trains has prokinetic effects on colonic contractions and transit in healthy dogs, mediated via the cholinergic and nitrergic pathways. Further clinical studies are warranted to explore the therapeutic potential of CES for slow colonic transit constipation.

Background Commensal bacteria such as probiotics that are neuroactive acutely affect the amplitudes of intestinal migrating motor complexes (MMCs). What is lacking for an improved understanding of these motility effects are region specific measurements of velocity and frequency. We have combined intraluminal pressure recordings with spatiotemporal diameter maps to analyze more completely effects of different strains of beneficial bacteria on motility. Methods Intraluminal peak pressure (PPr) was measured and video recordings made of mouse ex vivo jejunum and colon segments before and after intraluminal applications of Lactobacillus rhamnosus (JB-1) or Lactobacillus reuteri (DSM 17938). Migrating motor complex frequency and velocity were calculated. Key Results JB-1 decreased jejunal frequencies by 56% and 34% in colon. Jejunal velocities increased 171%, but decreased 31% in colon. Jejunal PPr decreased by 55% and in colon by 21%. DSM 17938 increased jejunal frequencies 63% and in colon 75%; jejunal velocity decreased 57%, but increased in colon 146%; jejunal PPr was reduced 26% and 12% in colon. TRAM-34 decreased frequency by 71% and increased velocity 200% for jejunum, but increased frequency 46% and velocity 50% for colon; PPr was decreased 59% for jejunum and 39% for colon. Conclusions & Inferences The results show that probiotics and other beneficial bacteria have strain and region-specific actions on gut motility that can be successfully discriminated using spatiotemporal mapping of diameter changes. Effects are not necessarily the same in colon and jejunum. Further research is needed on the detailed effects of the strains on enteric neuron currents for each gut region.

The gut microbiota is a complex consortium of microorganisms with the ability to influence important aspects of host health and development. Harnessing this ‘microbial organ’ for biomedical applications requires clarifying the degree to which host and bacterial factors act alone or in combination to govern the stability of specific lineages. To address this we combined bacteriological manipulation and light sheet fluorescence microscopy to monitor the dynamics of a defined two-species microbiota within the vertebrate gut. We observed that the interplay between each population and the gut environment produced distinct spatiotemporal patterns. Consequently, one species dominates while the other experiences dramatic collapses that are well fit by a stochastic mathematical model. Modeling revealed that bacterial competition could only partially explain the observed phenomena, suggesting that a host factor is also important in shaping the community. We hypothesized the host determinant to be gut motility, and tested this mechanism by measuring colonization in hosts with enteric nervous system dysfunction due to mutation in the Hirschsprung disease locus ret. In mutant hosts we found reduced gut motility and, confirming our hypothesis, robust coexistence of both bacterial species. This study provides evidence that host-mediated spatial structuring and stochastic perturbation of communities along with bacterial competition drives population dynamics within the gut. In addition, this work highlights the capacity of the enteric nervous system to affect stability of gut microbiota constituents, demonstrating that the ‘gut-brain axis’ is bidirectional. Ultimately, these findings will help inform disease mitigation strategies focused on engineering the intestinal ecosystem.

Chronic constipation is a prevalent, burdensome gastrointestinal disorder whose aetiology and pathophysiology remains poorly understood and is most likely multifactorial. Differences in the composition of the intestinal microbiota have been demonstrated when constipated patients and healthy controls have been compared. Growing evidence indicates that alterations of intestinal microbiota may contribute to constipation and constipation-related symptoms. The intestinal microbiota is a collection of microorganisms that live within the gastrointestinal tract, and perform many important health-promoting functions. The intestinal microbiota aids in the breakdown of food products into absorbable nutrients, stimulates the host immune system, prevents growth of pathogenic bacteria and produces a great variety of biologically important compounds. In this review, we will summarize the current evidence supporting roles of the intestinal microbiota in the pathogenesis and management of chronic constipation. The discussion will shed light on the novel mechanisms of intestinal microbiota and gut function interactions, which is invaluable in ultimately developing new therapeutic tools for the treatment of chronic constipation.

To understand the abnormalities that underpin functional gut disorders we must first gain insight into the normal patterns of gut motility. While detailed information continually builds on the motor patterns (and mechanisms that control them) of the human esophagus and anorectum, our knowledge of normal and abnormal motility in the more inaccessible regions of the gut remains poor. This particularly true of the human colon. Investigation of in vivo colonic motor patterns is achieved through measures of transit (radiology, scintigraphy and, more recently, “smart pills”) or by direct real-time recording of colonic contractility (intraluminal manometry). This short review will provide an overview of findings from the past and present and attempt to piece together the complex nature of colonic motor patterns. In doing so it will build a profile of human colonic motility and determine the likely mechanisms that control this motility.

Two experiments were conducted to test the following hypothesis: exposing broiler chickens to coarse insoluble fiber in the diet will result in enhanced gizzard function and performance, improved adaptability to an intermittent feeding program, and an increase in the occurrence of reverse peristalsis. In experiment 1, 102 Ross 308 broiler chickens were either intermittently or ad libitum fed a basal diet, the basal diet diluted with 15% coarse hulls (consisting of equal weights of hulls from oats and barley), or the basal diet diluted with 15% of the same hulls finely ground in a 2 × 3 factorial arrangement with 17 individually caged birds per treatment. Birds fed ad libitum had access to feed continuously for 18 h/d, whereas those on intermittent feeding had restricted access to feed from 7 d of age. From 18 d of age, the restrictive-feeding program consisted of four 1-h meals and one 2-h meal per day. In experiment 2, 156 broiler chickens in 12 pen cages with wood shaving-lined floors were exposed to 1 of 4 treatment groups with 3 pens/treatment: intermittent or ad libitum feeding of a basal diet and intermittent or ad libitum feeding of a coarse hull diet, as described above. At 31 and 32 d of age, birds in experiment 1 were inoculated with chromium EDTA via the cloaca. There was no interaction between diet and feeding regimen. The addition of hulls increased gizzard weight and content and lowered (P < 0.001) gizzard pH, but it had no effect on the ability of the birds to handle intermittent feeding. Despite the dilution with coarse hulls, weight gain and the gain:feed ratio were not affected, which could partly be explained by an increased (P < 0.001) starch digestibility. Dietary reflux was confirmed by the presence of chromium in all intestinal tract sections. Broilers exhibited reverse peristaltic contractions of sufficient magnitude to propel the marker from the cloaca to the gizzard.

Constipation is a particularly troublesome complaint in the elderly yet it is usually considered to be a simple management issue. Therefore physicians' lack of interest in and inadequate training about the etiology of constipation may contribute to their inability to manage the problem of constipation effectively. Constipation can become a chronic problem, refractory to management, and most likely the result of lifelong patterns of bowel and dietary habits and laxative use, along with the interaction of pathophysiological and perhaps senescent changes of gut motility. This article reviews the types and causes of constipation and the management of the problem in the elderly.

Previous patterns of energy intake influence gastrointestinal function and appetite, probably reflecting changes in small-intestinal nutrient-mediated feedback. Obese individuals consume more fat and may be less sensitive to its gastrointestinal and appetite-suppressant effects than lean individuals.To evaluate the hypothesis that, in obese individuals, the effects of duodenal fat on gastrointestinal motor and hormone function, and appetite would be enhanced by a short period on a very-low-calorie diet (VLCD).Eight obese men (body mass index 34±0.6 kg m(-2)) were studied on two occasions, before (V1), and immediately after (V2), a 4-day VLCD. On both occasions, antropyloroduodenal motility, plasma cholecystokinin (CCK), peptide-YY (PYY) and ghrelin concentrations, and appetite perceptions were measured during a 120-min intraduodenal fat infusion (2.86 kcal min(-1)). Immediately afterwards, energy intake was quantified.During V2, basal pyloric pressure and the number and amplitude of isolated pyloric pressure waves (PWs) were greater, whereas the number of antral and duodenal PWs was less, compared with V1 (all P0.05). Moreover, during V2, baseline ghrelin concentration was higher; the stimulation of PYY and suppression of ghrelin by lipid were greater, with no difference in CCK concentration; and hunger and energy intake (kJ; V1: 4378±691, V2: 3634±700) were less (all P0.05), compared with V1.In obese males, the effects of small-intestinal lipid on gastrointestinal motility and some hormone responses and appetite are enhanced after a 4-day VLCD.

The gut microbiota is integral to an organism’s digestive structure and has been shown to play an important role in producing substrates for gluconeogenesis and energy production, vasodilator, and gut motility. Numerous studies have demonstrated that variation in diet types is associated with the abundance and diversity of the gut microbiota, a relationship that plays a significant role in nutrient absorption and affects gut size. The Expensive-Tissue Hypothesis states (ETH) that the metabolic requirement of relatively large brains is offset by a corresponding reduction of the other tissues, such as gut size. However, how the trade-off between gut size and brain size in vertebrates is associated with the gut microbiota through metabolic requirements still remains unexplored. Here, we review research relating to and discuss the potential influence of gut microbiota on the ETH.

BACKGROUND: The microbiome-gut-brain axis is a bidirectional network that influences brain chemistry and behaviour. Antibiotics are known to alter several aspects of gut-brain signaling but the underlying mechanisms remain equivocal. As prior assessments of these mechanisms have been limited to changes in gut microbiota, we hypothesized that antibiotics may directly modulate neurons and neural reflexes. AIMS: To identify whether transient exposure of the gastrointestinal tract to antibiotics can acutely modulate peristaltic reflexes that depend on the enteric nervous system (ENS). METHODS: 4 cm colon segments excised from adult male Swiss Webster mice were submerged in an organ bath chamber (34°C oxygenated Krebs buffer solution) and cannulated at both the oral and anal ends. Gut lumens were perfused with Krebs saline control followed by either Krebs diluted Bacitracin (1, 3 or 10 mM) or Penicillin V (3, 10, 30 or 100 mM). Gut motility was recorded by video which was subsequently converted to spatiotemporal diameter maps for quantitative analysis. Paired t-tests were performed for before and after measurements. RESULTS: Alterations in ENS-dependent propagating contractile cluster (PCC) velocity and frequency were evoked by Bacitracin at concentrations of 1, 3 and 10 mM and Penicillin V above 10 mM. For Bacitracin, PCC velocity (mm/s) increased from 0.23 ± 0.06 to 0.35 ± 0.13 (n=20, P10 mM Penicillin V. PCC velocity (mm/s) increased from 0.21 ± 0.05 to 0.22 ± 0.04 (n=20, P=0.15) at 10 mM, 0.17 ± 0.04 to 0.54 ± 0.2 (n=16, P

Purpose of review Motility disturbances often occur in critically ill patients resulting in an increased rate of morbidity and mortality. Only limited options for treatment of gastrointestinal dysfunction have been introduced. Factors contributing to motility disorders in the ICU patient, and recent therapeutic approaches are reviewed in the following. Recent findings Despite the growing use of early enteral nutrition in the ICU and improvements in patients' outcome, feed intolerance and motility disorders in critical illness remain unsolved. Evaluation of pathophysiological patterns such as antro-pyloric dysfunction has led to a better knowledge of gut function, whereas development of new prokinetic agents is scarce, and enthusiasm has been cut by the withdrawal of some propulsive agents from the market. Summary The complexity of gastrointestinal motor function poses a challenge to the pharmacological modulation of gut motility. There has been progress in the understanding of pathophysiologic patterns, whereas therapeutic options are still rare. Metoclopramide and erythromycin are the best evaluated and still the most promising prokinetic agents. Only a few studies in critical illness are available, and the definite value of novel propulsive agents such as motilin agonists and μ-receptor antagonists is unclear due to small patient populations. The most reasonable approach of motility disorders in critical illness seems to be an individual assessment of all associated risk factors combined with early enteral nutrition and use of prokinetic agents.

James Lubawski, Theodore SaclaridesSection of Colon and Rectal Surgery, Rush University Medical Center, Chicago, IL, USAAbstract: Postoperative Ileus (POI) is a frequent, frustrating occurrence for patients and surgeons after abdominal surgery. Despite significant research investigating how to reduce this multi-factorial phenomenon, a single strategy has not been shown to reduce POI’s significant effects on length of stay (LOS) and hospital costs. Perhaps the most significant cause of POI is the use of narcotics for analgesia. Strategies that target inflammation and pain reduction such as NSAID use, epidural analgesia, and laparoscopic techniques will reduce POI but are accompanied by a simultaneous reduction in opioid use. Pharmacologic means of stimulating gut motility have not shown a positive effect, and the routine use of nasogastric tubes only increases morbidity. Recent multi-site phase III trials with alvimopan, a peripherally acting mu-antagonist, have shown significant reductions in POI and LOS by 12 and 16 hours, respectively, by blunting the effects of narcotics on gut motility while sparing centrally mediated analgesia. Use of alvimopan, along with a multi-modal postoperative treatment plan involving early ambulation, feeding, and avoiding nasogastric tubes, will likely be the crux of POI treatment and prevention.Keywords: postoperative ileus, alvimopan, abdominal surgery

Bioavailability is the fraction of an administered dose that reaches the systemic circulation. Health claims for functional foods can only be made if the ingredient reaches the target site to trigger the physiological action, hence substantiation requires good bioavailability. This is also expressed in the European Regulation on Health Claims. Albeit not new at all, a full understanding of the controlling factors for bioavailability in foods is still lacking. Foods are complex systems and can be part of a meal. The impact of product composition and the interplay with human physiology during fed or fasted state has to be understood: a functional ingredient has to be released from the product matrix into a molecularly dispersed state, either in classic solution or in micellar state. Only in the dispersed state can actives cross the gut wall. Release and dissolution are depending on both molecular physicochemical properties of the active and those of the entire product. More complex is the uptake of hydrophobic, poorly water-soluble substrates. As they do not dissolve in the aqueous intestinal environment, presence of fat, release of bile, enzymes, and gut motility to induce lipolysis are required. Surface-active bile salts together with lipolysis products create micelles containing the hydrophobic active. This imposes limitations on the formulation space for hydrophobic compounds. Finally, many ingredients are not fit for straightforward use as they compromise the stability or sensory characteristics of the product. Compartmentalization strategies, like encapsulation, may offer solutions to the problem; it should, however, not be forgotten that encapsulates themselves may effect bioavailability through the changed dynamics of the uptake processes. To explore and build a better understanding of these factors, a range of models are available and used in product formulation and claim substantiation. A structured approach and the selection of proper models will help to improve functional food formulations in the future.

m c ( t o o T he impetus for this issue comes from a Topic Symposium entitled, “Infant Feeding: Initiation, Problems, Approaches” held at the Peditric Academic Societies meeting in Toronto May 6, 007. The symposium focused on four aspects of eeding infants and young children. Each aspect was iscussed by an authority in the field. One presentation concerned the developmental spects of swallowing and feeding infants and oung children. Another addressed the development f gut motility in the premature infant and its elationship to enteral feeding. The third topic oncerned the behavioral treatment of feeding disrders in toddlers and finally, feeding issues related o neurologically impaired children were reviewed. Feeding premature and full-term infants through he first few years of life has become an area of nterest and study over the past two decades. The ealization that some infants and children are not fed asily or may develop feeding problems resistant to raditional approaches has led to the institution of eeding teams at larger pediatric centers. Hopefully, nformation presented at the Topic Symposium and ontained within this issue will be shared with thers as we follow emerging research concerning he optimal feeding of normal infants and children, nd those with feeding disorders.

The National Institute of Child Health and Human Development and the Digestive Diseases Interagency Coordinating Committee held a workshop, chaired by Dr. W. Allan Walker, on July 10-11, 2006, to identify promising leads in necrotizing enterocolitis (NEC) research. The goals of the workshop were to identify new approaches to the prevention and treatment of NEC, to define basic and translational mechanisms of potential approaches to NEC, and to develop recommendations for clinical studies to reduce the incidence of NEC. Workshop participants implicated prematurity, introduction of enteral feedings, gastrointestinal bacterial colonization, gut motility, proinflammatory cytokines, impaired gut blood flow, and various neonatal complications in the pathogenesis of NEC. They concluded that a unifying hypothesis encompassing these pathogenetic factors is the uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants. The inflammatory cascade appears to offer multiple targets for interventions with a variety of anti-inflammatory agents, including human milk and probiotics. Because of the rapidity with which the inflammatory response gets out of control in infants with NEC, workshop participants agreed that searching for ways to prevent NEC will be more rewarding than trying to identify ways to treat the condition once it has become established.

Gut peptides and their receptors are becoming of more interest as possible drug targets because the physiological role of these peptides is becoming increasingly clear. The glucagon-like peptides have physiological roles in glucose homeostasis, appetite regulation and intestinal proliferation. The PP family similarly plays a role in appetite regulation, thus making these peptides a possible target for the treatment of obesity and metabolic disease. Ghrelin, in contrast to the previously mentioned peptides stimulates appetite and gut motility, making it a target for drugs improving gut motility.

Irritable bowel syndrome (IBS) is a common gastrointestinal condition whose cause remains unknown. Therefore, most of our effort in treating IBS has been based on a symptom approach. Recent evidence is beginning to suggest that subjects with IBS may have an alteration in gastrointestinal flora. Specifically, findings suggest that IBS patients have excessive bacteria in the small bowel, known as bacterial overgrowth. Although diagnostic testing for bacterial overgrowth is somewhat controversial, as there is no true gold standard test for bacterial overgrowth, antibiotic-based therapies for IBS are now shown to be very effective in treating IBS. Follow-up work in this area has even begun to demonstrate associative factors between gut bacteria and IBS that may explain the different types of IBS. The best example of this is the finding that methanogenic organisms in IBS patients are wholly associated with constipation-predominant IBS. It seems that the methane gas emitted during fermentation may have an influence on gut motility. In this review, the evidence for gut ecology associations in IBS is presented. A treatment algorithm also is proposed based on these findings. New areas of research in IBS such as gut bacteria are changing the treatment approach in IBS from a symptom-based style to one that is hypothesis driven.