Human Intestinal Motility Research Articles

Simulating human gastrointestinal motility in dynamic in vitro models.

The application of dynamic in vitro gastrointestinal (GI) models has grown in popularity to understand the impact of food structure and composition on human health. Given that GI motility is integral to digestion and absorption, a predictive in vitro model should faithfully replicate the motility patterns and motor functions in vivo. In this review, typical characteristics of gastric and small intestinal motility in humans as well as the biomechanical and hydrodynamic events pertinent to gut motility are summarized. The simulation of GI motility in the presently existing dynamic in vitro models is discussed from an engineering perspective and categorized into hydraulic, piston/probe-driven, roller-driven, pneumatic, and other systems. Each system and its representative models are evaluated in terms of their motility patterns, the key hydrodynamic characteristics concerning gut motility, their performance in simulating the key physiological events, and their ability to establish in vitro-in vivo correlations. Practical Application: The review paper provided useful information in the design of dynamic GI models and the simulation of human gastric and small intestinal motility which are important for understanding food and health.

388 Effects of the Herbal Drug STW 5 and Its Individual Components on Human Intestinal Motility

388 Effects of the Herbal Drug STW 5 and Its Individual Components on Human Intestinal Motility

Role of cannabinoid receptors in the control of gastrointestinal motility and perception

The identification of endocannabinoids and cannabinoid CB1 receptors in key areas of the intestinal wall, such as cholinergic neurons, supports a role for cannabinoids in the control of gastrointestinal motility. Activation of CB1 receptors inhibits the peristaltic reflex and slows down gastrointestinal and colonic transit. Endocannabinoids play an important inhibitory role in the control of the occurrence of transient lower esophageal sphincter relaxations. Cannabinoid receptor agonists inhibit gastric emptying and intestinal motility in humans. There is strong anatomical support for a role of CB1 receptors in the control of gastrointestinal perception, since these receptors have been identified in key sites of the neuronal circuitry involved in the transmission of visceral pain. Experimental data indicate a visceral antinociceptive action of cannabinoid receptor agonists, which remains to be confirmed in humans.

The macrophage system in the intestinal muscularis externa during inflammation: an immunohistochemical and quantitative study of osteopetrotic mice

Intestinal inflammation results in disturbed intestinal motility in humans as well as in animal models. This altered function of smooth muscle cells and/or the enteric nervous system may be caused by activation of macrophages in muscularis externa and a thereby following release of cytokines and chemokines that causes influx of mononuclear cells and neutrophilic granulocytes. We subjected osteopetrotic (op/op) mice that lack certain macrophage subtypes, e.g. macrophages in the muscularis externa and +/+ mice to LPS to induce inflammatory cell influx. The densities of F4/80+, MHCII+, and myeloperoxidase+ cells were quantified using stereological sampling. In +/+ mice we found that MHCII+ cells outnumber F4/80+ cells and that LPS injection increased the density of MHCII+ cells temporarily but not that of F4/80+ cells. This indicates that an upregulation of MHCII antigen takes place and that two or more macrophage subtypes with comparable morphologies exist. Osteopetrotic mice lacked MHCII+, CD169+, and F4/80+ cells after either treatment, which indicate that these cells are CSF-1-dependent. LPS induced VCAM-1 activation of the vessels, modest influx of granulocytes, as well as an iNOS-activation in a cell type different from macrophages in both +/+ and op/op mice.

Identification of the slow wave component of the electroenterogram from Laplacian abdominal surface recordings in humans

The electroenterogram (EEnG) is a surface recording of the myoelectrical activity of the smooth muscle layer of the small intestine. It is made up of two signals: a low-frequency component, known as the slow wave (SW), and high-frequency signals, known as spike bursts (SB). Most methods of studying bowel motility are invasive due to the difficult anatomic access of the intestinal tract. Abdominal surface EEnG recordings could be a noninvasive solution for monitoring human intestinal motility. However, surface EEnG recordings in humans present certain problems, such as the low amplitude of the signals and the influence of physiological interference such as the electrocardiogram (ECG) and respiration. In this study, a discrete estimation of the abdominal surface Laplacian potential was obtained using Hjorth's method. The objective was to analyze the enhancement given by Laplacian EEnG estimation compared to bipolar recordings. Eight recording sessions were carried out on eight healthy human volunteers in a state of fasting. First, the ECG interference content present in the bipolar signals and in the Laplacian estimation were quantified and compared. Secondly, to identify the SW component of the EEnG, respiration interference was removed by using an adaptive filter, and spectral estimation techniques were applied. The following parameters were obtained: the dominant frequency (DF) of the signals, stability of the rhythm (RS) of the DF detected and the percentage of DFs within the typical frequency range for the SW (TFSW). Results show the better ability of the Laplacian estimation to attenuate ECG interference, as compared to bipolar recordings. As regards the identification of the SW component of the EEnG, after removing respiration interference, the mean value of the DF in all abdominal surface recording channels and in their Laplacian estimation ranged from 0.12 to 0.14 Hz (7.3 to 8.4 cycles min−1 (cpm)). Furthermore in 80% of the cases, the detected DFs were inside the typical human SW frequency range, and the ratio of frequency change in the surface bipolar and Laplacian estimation signals, in 90% of the cases, was within the frequency change accepted for human SW. Significant statistical differences were also found between the DF of all surface signals (bipolar and Laplacian estimation) and the DF of respiration. In conclusion, it was demonstrated that the discrete Laplacian potential estimation attenuated the physiological interference present in bipolar surface recordings, especially ECG. Furthermore, a slow frequency component, whose frequency, rhythm stability and amplitude fitted with the SW patterns in humans, was identified in bipolar and Laplacian estimation signals. This could be a useful non-invasive tool for monitoring intestinal activity by abdominal surface recordings.

Small intestinal motility

To review recently published studies presenting novel and relevant information on small intestinal motility in humans and animals. Mechanisms of intestinal dysmotility in patients with pseudoobstruction and colonic inertia are becoming better clarified. The role of enteric flora in health and disease is an important and rapidly evolving area that will no doubt yield significant advances in the evaluation and treatment of many digestive disorders. The role of bacterial overgrowth in irritable bowel syndrome requires further study. The mechanisms underlying postoperative ileus are becoming both better understood and increasingly complex. Peripheral opioid antagonists may represent an important therapeutic advance in the treatment of ileus. Cannabinoids also appear to play a role in ileus and this echoes our rapidly evolving understanding of these compounds in the regulation of motility. Small intestinal motility remains an understudied area. Recent publications have shed additional light on myogenic, neural, and hormonal control mechanisms.

An Abnormal Distribution of C-Kit Positive Cells in the Normoganglionic Segment Can Predict a Poor Clinical Outcome in Patients with Hirschsprung's Disease

The loss or decrease of interstitial cells of Cajal (ICCs) has been implicated in several disorders of human intestinal motility. We have encountered a few cases suffering from severe constipation or enterocolitis resulting in patient death after a definitive operation for HD, even though the normoganglionic intestine had been successfully pulled through. We investigated the distribution of ICCs using c-kit immunostaining in the normoganglionic segment and compared these findings with the clinical outcome after a definitive operation in each case. The distributions of ICCs were investigated by using c-kit immunostaining in the normoganglionic segment in the resected bowel in 15 cases with HD. The distributions of protein gene product 9.5 (PGP 9.5) as a general neuronal marker and those of NADPH-diaphorase (NADPH-d) as a marker of nitric-oxide neurons were also examined. The numbers of ICCs and neurons were evaluated quantitatively. The histopathological results were compared with the clinical outcome after definitive operation in each case. C-kit immunoreactive cells showed a normal distribution in the normoganglionic segment in 13 cases, while they were markedly (less than 50% compared with the other cases) decreased in 2 cases. The distributions of PGP 9.5 and NADPH-d were almost the same in all cases. The bowel movements of 13 cases showing normal c-kit distribution were satisfactory. In contrast, the bowel movements were impaired in 2 cases with a decreased number of c-kit positive cells. One infant suffered from severe persistent constipation and thus had to undergo a resection of a dilated colon. The other infant died of sepsis due to postoperative enterocolitis and showed a markedly dilated colon. A decreased number of c-kit positive cells in the normoganglionic segment can thus allow us to predict a poor clinical outcome after definitive surgery, probably due to poor intestinal motility. Therefore examining the c-kit distribution in a resected bowel specimen in patients with HD should be mandatory in order to select the optimal postoperative treatment regimen for each case.

Small intestinal motility

To review recently published studies presenting novel and relevant information on small intestinal motility in humans and animals. The reviewed studies covered a variety of topics with several themes emerging. The relation between bacterial overgrowth and altered intestinal motility gathers support in a variety of conditions including portal hypertension and senescence. The mechanisms of postoperative ileus are becoming better understood. Cannabinoids play an important role in ileus and this further highlights the importance of these compounds in intestinal motility. Luminal impedance appears to be an important tool for investigation of intestinal flow. Small intestinal motility remains an understudied area. Recent publications have shed additional light on myogenic, neural, and hormonal control mechanisms. Novel investigative techniques will likely further improve our understanding.

Do Elevated Plasma Vasoactive Intestinal Polypeptide (VIP) Levels Cause Small Intestinal Motor Disturbances in Humans?

Increased VIP plasma levels cause severe secretory diarrhea. Moreover, VIP is a major regulator of human intestinal motility. We hypothesized that VIP-mediated intestinal motility disturbances contribute to symptoms in elevated plasma VIP. Ten healthy volunteers were intubated twice with an orojejunal multilumen tube for duodenal manometry, jejunal perfusion of electrolyte and marker solution, and aspiration 10 and 40 cm more distally. All subjects randomly received intravenous infusion of saline and 300 pmol/kg x hr VIP for 5 hr. Results showed that VIP but not saline infusion induced netjejunal sodium secretion, watery diarrhea, and cardiovascular effects (P < 0.04). VIP did not alter intestinal motor activity or the mean duration of the interdigestive motility cycle or of phases I and II but nearly halved the duration of phase III (P = 0.0002). We conclude that increased plasma VIP markedly shortens human phase III activity without influencing other motility parameters. Hence, it is unlikely that VIP-mediated small intestinal motor disturbances cause symptoms in VIPOMA. Yet VIP may contribute to terminate phase III motility.

Endogenous nitric oxide modulates small intestinal nutrient transit and activity in healthy adult humans

Objective. Nitric oxide (NO) mechanisms have been shown to modulate fasting small intestinal motility in humans, but a role in the regulation of human postprandial small intestinal motility has not been assessed. The aim of this study was to evaluate the effect of the NO synthase inhibitor NG-monomethyl-l-arginine (l-NMMA) on the regulation of small intestinal nutrient transit and postprandial small intestinal motility in healthy humans. Material and methods. Seven healthy male volunteers (18–27 years) underwent antroduodenal manometry recordings for 4 h on 2 occasions after intraduodenal instillation of a 500 KJ [120 Kcal] test meal. The meal was administered 15 min after the commencement of a 60-min intravenous infusion of l-NMMA (4 mg kg−1 h−1) or saline (0.9%). Studies were separated, performed in randomized order and >3 days apart. The frequency and amplitude of duodenal pressure waves together with time to return of fasting motility (phase III) was determined. On each day, small intestinal transit was measured using a lactulose breath test. Results. The test meal interrupted fasting small intestinal motility in all subjects. The time to recurrence of fasting motility following its postprandial disruption was similar (l-NMMA versus saline 1.6±0.2 h versus 1.9±0.1 h; p>0.05). Duodenocaecal transit was delayed by infusion of l-NMMA compared with saline (l-NMMA versus saline 92.1±3.9 min versus 66.4±6.4 min; p<0.005). Infusion of l-NMMA significantly increased the frequency (l-NMMA versus saline 50.4±6.6 versus 34.8±5.5 waves per 30 min; p<0.05) and amplitude (l-NMMA versus saline 20.4±1.5 versus 15.5±1.1 mmHg; p<0.01) of duodenal pressure waves. Conclusions. These data suggest that endogenous NO may play a role in the regulation of small intestinal nutrient transit by regulating small intestinal motility in healthy individuals.

Small intestinal motility

In the past year, many studies were published in which new and relevant information on small intestinal motility in humans and laboratory animals was obtained. Although the reported findings are heterogeneous, some themes appear to be particularly interesting and novel. Among these is the association between disordered small intestinal motility and bacterial overgrowth of the small intestine. Studies in patients with portal hypertension, in patients with chronic renal failure, and in a rat model of experimental acute pancreatitis all point in the same direction. Another topic of particular interest is the relation between duodenal motility and glucose absorption; propagated duodenal pressure wave sequences are positively related to glucose absorption. Finally, many studies addressed the mechanisms involved in the regulation of interdigestive and postprandial small intestinal motility. These confirmed the key role of cholecystokinin and provided new information on the role of orexin A and leptin. The new information on intestinal motility gathered in the past year provides a greater insight in the pathophysiology of a number of diseases and will stimulate further studies in laboratory animals and in human subjects.

Role of endogenous nitric oxide in regulating antropyloroduodenal motility in humans

OBJECTIVES: Previously we demonstrated the involvement of nitric oxide (NO) in the regulation of interdigestive small intestinal motility in humans. The role of NO in postprandial motility remains to be studied. Therefore, we investigated the effect of the NO synthase inhibitor N G-monomethyl- l-arginine (L-NMMA) on antral, pyloric, and small intestinal postprandial motility in healthy volunteers. METHODS: Ten healthy male volunteers (ages 19–29 yr) underwent stationary antropyloroduodenal manometry recording during administration of a placebo or a high dose of L-NMMA (12 mg/kg within 5 min, followed by a maintenance infusion of 6.7 mg/kg/h i.v.) in a double blind, randomized order. Motility was recorded before and after ingestion of a 300-kcal liquid meal. RESULTS: Two and a half minutes (±0.4 min) after infusion of L-NMMA, rapidly propagated phase III-like activity was observed in the proximal duodenum in every subject. Mean propagation velocity was 26 ± 5 cm/min. The duration of the phase III-like activity increased proximally (9.2 ± 1.6 min) to distally (12 ± 1.5 min), whereas the frequencies of contractions were similar in all manometric channels (10.8 ± 0.3/min). Postprandial duodenal motility was disrupted by phase III-like activity in four of 10 subjects (15–58 min after the meal) during L-NMMA infusion, but not during placebo. Antral or pyloric motility and basal pyloric tone were not significantly altered by L-NMMA, relative to the placebo. CONCLUSIONS: We showed that inhibition of NO biosynthesis triggers the onset of a rapidly propagating phase III and shortens the postprandial period, indicating that NO is involved in the modulation of fasting and postprandial small intestinal motility in humans.

HOX11L1: a promoter study to evaluate possible expression defects in intestinal motility disorders

Intestinal Neuronal Dysplasia (IND) is a congenital disorder characterized by intestinal motility defects associated with hyperplasia of enteric ganglia. A phenotype resembling human IND has been observed in mice knocked-out for a member of the Hox11 homeobox gene family, Hox11l1, suggesting that the human homologue of this gene could be responsible for congenital disorders of intestinal innervation. However, previous mutation analysis of the coding sequence of the HOX11L1 gene in patients affected with IND detected neither mutations nor other nucleotide variants. In the present work, a detailed study of the non coding promoter region of this gene was undertaken in patients affected with IND, with Hirschsprung associated IND and with neurogenic chronic intestinal pseudo-obstruction. No alterations potentially impairing expression of HOX11L1, such as nucleotide variants, small deletions or cytogenetic alterations, could be identified thus further excluding the direct involvement of this gene in the pathogenesis of human intestinal motility disorders.

Circadian coupling between pancreatic secretion and intestinal motility in humans.

Human interdigestive intestinal motility follows a circadian rhythm with reduced nocturnal activity, but circadian pancreatic exocrine secretion is unknown. To determine whether circadian changes in interdigestive pancreatic secretion occur and are associated with motor events, pancreatic enzyme outputs, proximal jejunal motility, and plasma pancreatic polypeptide concentrations were measured during consecutive daytime and nighttime periods (12 h each) in seven healthy volunteers using orojejunal multilumen intubation. Studies were randomly started in the morning or evening. Nocturnally, motility decreased (motor quiescence: 67 +/- 22 vs. 146 +/- 37 min; motility index: 3.59 +/- 0.33 vs. 2.78 +/- 0.40 mmHg/min; both P < 0.05) but amylase output increased (273 +/- 78 vs. 384 +/- 100 U/min; P < 0.05) and protease output remained unchanged (P > 0.05); consequently, enzyme/motility ratio increased. Amylase outputs were always lowest during phase I. Motor but not pancreatic circadian activities were associated with sleep. Pancreatic polypeptide plasma concentrations were unchanged. Consequently, intestinal motor and pancreatic exocrine functions may have different circadian rhythms, i.e., decreased motor and stable secretory activity during the night. However, the association between individual phases of interdigestive motor and secretory activity is preserved. The nocturnal increase in enzyme/motility ratio is probably not caused by increased cholinergic tone.

Postoperative Recovery Patterns from Postoperative Ileus and Influence of Epidural Morphine on Human Intestinal Motility and Effectiveness of Hormone after Surgery

We investigate the recovery patterns of intestinal motility following postoperative ileus and evaluated the influences of epidural morphine administration (which is used to relieve the postoperative pain after abdominal surgery) on the migrating motor complexes (MMC) by using manometry and clinical assessment. The mean appearance time of MMC was 9.3 hours after surgery, and the cycle increased gradually with time. Clinical recovery signs (audible detection of bowel sounds and passage of flatus) of intestinal motility after surgery were confirmed later than the changes in MMC. Morphine induced premature-MMC waves higher in amplitude and longer in duration than spontaneous MMC. After the premature-MMC was induced by morphine, the spontaneous MMC with qualities similar to that observed before injection of morphine was reappeared. Serum concentrations of motilin and secretin were not changed by the morphine injection. These observations suggest that epidural morphine induced premature contractile activities may not be mediated any hormones but may be induced via gut opioid receptors. The morphine-induced contractions of intestine were distinct in pattern from the intestinal activity following postoperative ileus.

Evidence that nitric oxide mechanisms regulate small intestinal motility in humans

BackgroundNon-cholinergic non-adrenergic neural mechanisms involving nerves containing NO have been shown to modulate smooth muscle in the gastrointestinal tract, and it has been suggested that release from tonic NO inhibition...

Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome

Background—Corticotropin-releasing hormone (CRH) plays a key role in modulating intestinal motility in stressed animals.Aims—To evaluate the effect of CRH on intestinal motility in humans and to determine whether patients with...

Response of the human intestine to high volume infusion.

The motor patterns and luminal capacity of the human intestine should affect symptoms and resorption during pathological, massive small intestinal flow. Little is known of human intestinal motility in this situation. This study aimed at mimicking secretory diarrhoea (experimentally) in healthy volunteers by intrajejunal infusion of a non-absorbable iso-osmotic solution at 20 ml/min. During the infusion intraluminal jejunal pressures and small intestinal transit times were measured. The infusion initially caused jejunal contractile activity similar to that of the fed state but this was replaced by discrete clusters of contractions (DCCs) after 29.1 ((SEM) 8.2) minutes. DCCs each lasted 38 ((SEM) 0.8 seconds) and were associated with colicky abdominal discomfort. Later, after 1400-1800 ml had been infused, distal jejunal pressure waves fell to 10 mm Hg or less. Frequent fasting DCCs predicted earlier onset and more frequent DCCs during the infusion. Thus, the rate and volume of flow during simulated secretory diarrhoea determine the pattern of the small bowel pressure profile; eventually, a volume load is reached in which the small bowel acts as a poorly segmenting conduit resulting in very fast transit rates.

Changes in esophageal wall layers during motility: measurements with a new miniature ultrasound suction device.

We have developed a miniaturized ultrasound device that attaches to the gastrointestinal mucosa by suction and produces high-resolution (+/- 0.1 mm) images of the layers of the intestinal wall. The esophageal wall layers in a single sheep were measured during 20 occlusive contractions observed with simultaneous endoscopy, which revealed thickening of the inner circular muscle layer from 1.2 +/- 0.2 mm to 2.2 +/- 0.4 mm (p < 0.01), and during 20 dilations demonstrating thinning of the full thickness of the esophageal wall from 3.6 +/- 0.3 mm to 2.9 +/- 0.3 mm (p < 0.01). Safety experiments performed in two canine stomachs demonstrated no erosions or ulceration at any level of suction. Our investigations indicate that the M-mode suction ultrasound device can safely assess changes occurring in the layers of the esophageal wall during contractions and dilations and should be evaluated for the study of human intestinal motility.

Effect of age on human gastric and small bowel motility.

To test the hypothesis that age alters fasting and postprandial antral and intestinal motility in humans, we studied 23 patients, aged 18-39 years (median 28), and 13 patients, aged 40-69 years (median 49). All were having gastrointestinal symptoms, but in none was there objective clinical, radiologic, or endoscopic features of bowel disease, and manometry of the stomach and proximal small bowel was normal. We quantitated certain parameters of fasting intestinal motility and postprandial antral and jejunal motility. There were no significant differences in the interval between interdigestive motor complexes (IMC), duration, propagation velocity, or maximum number of contractions during phase III of the IMC, or postprandial antral and jejunal motility indices. The postprandial indices show a very similar distribution in each decade. Thus, in selected patients with unexplained gastrointestinal symptoms but no objective features of gut disease, quantifiable gastric and small bowel motility parameters do not differ in the age groups 18-39 and 40-69 years.