cholecystokinin and Irritable-Bowel-Syndrome

Traditional Chinese Medicine (TCM) serves as the most common alternative therapeutic approach for Western medicine and benefits IBS patients globally. Due to the lack of scientific evidence in the past, TCM formulas were not internationally well recognized as promising IBS remedies. In this review, firstly, we present the etiology and therapy of IBS in terms of traditional Chinese medical theory. Secondly, we summarize the clinical randomized controlled trials (RCTs) of TCM formulas for IBS patients that are available in the literature (from 1998 to September 2013), in which 14 RCTs conducted of high quality were discussed in detail. Of the 14 selected trials, 12 of those concluded that TCM formulas provided superior improvement in the global symptoms of IBS patients over the placebo or conventional medicines. As well, all 14 RCTs suggested that TCM formulas have good safety and tolerability. Last but not least, we explore the pharmacological mechanisms of the anti-IBS TCM formulas available in the literature (from 1994 to September, 2013). Collectively, in combating IBS symptoms, most TCM formulas exert multi-targeting actions including the regulation of neurotransmitters and hormones in the enteric nervous system (ENS), modulation of smooth muscle motility in the gastrointestinal (GI) tract, modulation of the hypothalamic-pituitary-adrenal (HPA) axis, attenuation of intestinal inflammation and restoration of intestinal flora, etc. In conclusion, TCM formulas appear to be promising for IBS treatment. This review provides a useful reference for the public in furthering a better understanding and acceptance of TCM formulas as IBS remedies.

Topics: Cholecystokinin; Drugs, Chinese Herbal; Gastrointestinal Motility; Humans; Hypothalamo-Hypophyseal System; Intestines; Irritable Bowel Syndrome; Medicine, Chinese Traditional; Muscle, Smooth; Neurotransmitter Agents; Nitric Oxide; Nitric Oxide Synthase Type II; Pituitary-Adrenal System; Randomized Controlled Trials as Topic; Serotonin; Signal Transduction; Somatostatin; Substance P; Vasoactive Intestinal Peptide

The treatment of irritable bowel syndrome due to the heterogeneous clinical symptoms and coexisting psychiatric disorders is still controversial. Although several agents with different mechanisms of action are widely used in clinical practice, there are only few drugs available with strong evidence of their efficacy, safety and tolerability at present. The etiology of irritable bowel syndrome is considered to be multifactorial: experimental and clinical research on visceral hypersensitivity, motility and brain-gut axis involving its neurotransmitters and receptors created the foundation of novel therapeutic approaches. Albeit nowadays several drugs (alosetron, tegaserod) have been registered in a few countries for the treatment of irritable bowel syndrome, further large clinical trials are required related to the new chemical entities.

Topics: Adrenergic alpha-Agonists; Analgesics, Opioid; Anti-Bacterial Agents; Antidepressive Agents; Carbolines; Chloride Channel Agonists; Cholecystokinin; Corticotropin-Releasing Hormone; Gastrointestinal Agents; Humans; Indoles; Irritable Bowel Syndrome; Muscarinic Antagonists; Neurokinin-1 Receptor Antagonists; Neurotrophin 3; Parasympatholytics; Probiotics; Receptors, Neurokinin-2; Serotonin Agents; Somatostatin

Irritable bowel syndrome (IBS) is characterized by gastrointestinal symptoms. Overweight and increased risk of metabolic syndromes/diabetes are observed in IBS, conditions associated with plasminogen activator inhibitor-1 (PAI-1) and visfatin. The aim of this study was to measure blood levels of AXIN1, cholecystokinin (CCK), enkephalin, ghrelin, neuropeptide Y (NPY), PAI-1, and visfatin before and after a 4-week intervention with a starch- and sucrose-reduced diet (SSRD). A total of 105 IBS patients were randomized to either SSRD (n = 80) or ordinary diet (n = 25). Questionnaires were completed, and blood was analyzed for AXIN1 and hormones. AXIN1 (p = 0.001) and active ghrelin levels (p = 0.025) were lower in IBS than in healthy volunteers at baseline, whereas CCK and enkephalin levels were higher (p < 0.001). In the intervention group, total IBS-symptom severity score (IBS-SSS), specific gastrointestinal symptoms, psychological well-being, and the influence of intestinal symptoms on daily life were improved during the study, and weight decreased (p < 0.001 for all), whereas only constipation (p = 0.045) and bloating (p = 0.001) were improved in the control group. PAI-1 levels tended to be decreased in the intervention group (p = 0.066), with a difference in the decrease between groups (p = 0.022). Visfatin levels were decreased in the intervention group (p = 0.007). There were few correlations between hormonal levels and symptoms. Thus, this diet not only improves IBS symptoms but also seems to have a general health-promoting effect.

Topics: Cholecystokinin; Diet; Enkephalins; Gastrointestinal Diseases; Ghrelin; Humans; Irritable Bowel Syndrome; Nicotinamide Phosphoribosyltransferase; Plasminogen Activator Inhibitor 1; Starch; Sucrose

Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS.. We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls.. Fasting plasma CCK levels were significantly elevated in patients (1.2+/-0.8 pM) compared with those in controls (0.8+/-0.7 pM, p=0.006), as was the incremental postprandial CCK response (72+/-73 versus 40+/-42 pM.60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215+/-135 versus 162+/-169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1+/-36.5 versus 60.8+/-25.1 versus 57.5+/-23.9 pM, one-way ANOVA p=0.003).. IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.

Topics: Adolescent; Adult; Age Factors; Aged; Biomarkers; Cholecystokinin; Fasting; Female; Follow-Up Studies; Humans; Intestine, Small; Irritable Bowel Syndrome; Male; Middle Aged; Motilin; Peptide YY; Postprandial Period; Psychotherapy; Radioimmunoassay; Retrospective Studies; Sex Factors

Altered gut regulation, including motor and secretory mechanisms, is characteristic of irritable bowel syndrome (IBS). The severity of postprandial symptoms in IBS patients is associated with discomfort and pain; gas-related symptoms such as bloating and abdominal distension; and abnormal colonic motility. The aim of this study was to assess the postprandial response, i.e., gut peptide secretion and gastric myoelectric activity, in patients with constipation-predominant IBS. The study was conducted on 42 IBS patients (14 males, 28 females, mean age 45.1 ± 15.3 years) and 42 healthy participants (16 males, 26 females, mean age 41.1 ± 8.7 years). The study assessed plasma gut peptide levels (gastrin, CCK-Cholecystokinin, VIP-Vasoactive Intestinal Peptide, ghrelin, insulin) and gastric myoelectric activity obtained from electrogastrography (EGG) in the preprandial and postprandial period (meal-oral nutritional supplement 300 kcal/300 ml). Mean preprandial gastrin and insulin levels were significantly elevated in IBS patients compared to the control group (gastrin: 72.27 ± 26.89 vs. 12.27 ± 4.91 pg/ml; p < 0.00001 and insulin: 15.31 ± 12.92 vs. 8.04 ± 3.21 IU/ml; p = 0.0001), while VIP and ghrelin levels were decreased in IBS patients (VIP: 6.69 ± 4.68 vs. 27.26 ± 21.51 ng/ml; p = 0.0001 and ghrelin: 176.01 ± 88.47 vs. 250.24 ± 84.55 pg/ml; p < 0.0001). A nonsignificant change in the CCK level was observed. IBS patients showed significant changes in postprandial hormone levels compared to the preprandial state-specifically, there were increases in gastrin (p = 0.000), CCK (p < 0.0001), VIP (p < 0.0001), ghrelin (p = 0.000) and insulin (p < 0.0001). Patients with IBS showed reduced preprandial and postprandial normogastria (59.8 ± 22.0 vs. 66.3 ± 20.2%) compared to control values (83.19 ± 16.7%; p < 0.0001 vs. 86.1 ± 9.4%; p < 0.0001). In response to the meal, we did not observe an increase in the percentage of normogastria or the average percentage slow-wave coupling (APSWC) in IBS patients. The postprandial to preprandial power ratio (PR) indicates alterations in gastric contractions; in controls, PR = 2.7, whereas in IBS patients, PR = 1.7, which was significantly lower (p = 0.00009). This ratio reflects a decrease in gastric contractility. Disturbances in the postprandial concentration of gut peptides (gastrin, insulin and ghrelin) in plasma may contribute to abnormal gastric function and consequently intestinal motility, which are manifested in the intens

Topics: Adult; Cholecystokinin; Female; Gastrins; Gastrointestinal Hormones; Ghrelin; Humans; Insulins; Irritable Bowel Syndrome; Male; Middle Aged; Postprandial Period; Vasoactive Intestinal Peptide

Ingestion of a meal frequently induces an urge to defaecate, the so-called gastro-colonic or gastro-rectal reflex. In patients with irritable bowel syndrome (IBS), symptoms are often provoked by meals. Cholecystokinin (CCK), a proximal gut peptide released after ingestion of a meal, may mediate these postprandial changes. The potential role of CCK in rectal sensory and motor function was evaluated by a rectal barostat study in healthy controls and patients with IBS. METHOD ; The sensory effects on serosal and mucosal receptors were studied. Twelve healthy controls and 12 patients with IBS underwent a ramp distension procedure of the rectum during infusion of CCK and placebo in random order. In 10 other healthy controls and 10 IBS patients an intermittent distension procedure was performed during infusion of CCK and placebo in random order.. No differences were found in rectal compliance during ramp distensions between IBS patients and controls. CCK did not affect perception of urge and pain in controls or in IBS patients. Similar results were obtained during the intermittent distensions, but at higher distension pressures CCK significantly increased rectal sensitivity in IBS patients.. Infusion of exogenous CCK to plasma levels normally seen in the postprandial state did not influence rectal motor function or sensations during ramp distension but it did significantly increase pain sensation in IBS patients during rapid intermittent distension.

Topics: Adult; Analysis of Variance; Case-Control Studies; Cholagogues and Choleretics; Cholecystokinin; Female; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Postprandial Period; Pressure; Prospective Studies; Rectum; Sensation; Visceral Pain; Young Adult

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut.

Topics: Adult; Aged; Biomarkers; Cholecystokinin; Chromogranin A; Endocrine Cells; Female; Gastroenterology; Gastrointestinal Tract; Guidelines as Topic; Humans; Inflammation; Intestines; Irritable Bowel Syndrome; Male; Middle Aged; Peptide YY; Prevalence; Serotonin

Coptis chinensis rhizomes (Coptidis Rhizoma, CR), also known as "Huang Lian", is a common component of traditional Chinese herbal formulae used for the relief of abdominal pain and diarrhea. Yet, the action mechanism of CR extract in the treatment of irritable bowel syndrome is unknown. Thus, the aim of our present study is to investigate the effect of CR extract on neonatal maternal separation (NMS)-induced visceral hyperalgesia in rats and its underlying action mechanisms.. Male Sprague-Dawley rats were subjected to 3-h daily maternal separation from postnatal day 2 to day 21 to form the NMS group. The control group consists of unseparated normal (N) rats. From day 60, rats were administrated CR (0.3, 0.8 and 1.3 g/kg) or vehicle (Veh; 0.5% carboxymethylcellulose solution) orally for 7 days for the test and control groups, respectively.. Electromyogram (EMG) signals in response to colonic distension were measured with the NMS rats showing lower pain threshold and increased EMG activity than those of the unseparated (N) rats. CR dose-dependently increased pain threshold response and attenuated EMG activity in the NMS rats. An enzymatic immunoassay study showed that CR treatment significantly reduced the serotonin (5HT) concentration from the distal colon of NMS rats compared to the Veh (control) group. Real-time quantitative PCR and Western-blotting studies showed that CR treatment substantially reduced NMS induced cholecystokinin (CCK) expression compared with the Veh group.. These results suggest that CR extract robustly reduces visceral pain that may be mediated via the mechanism of decreasing 5HT release and CCK expression in the distal colon of rats.

Topics: Abdominal Pain; Analgesics; Animals; Cholecystokinin; Colon; Coptis; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Electromyography; Hyperalgesia; Irritable Bowel Syndrome; Male; Maternal Deprivation; Muscle, Smooth; Pain Threshold; Phytotherapy; Rats; Rats, Sprague-Dawley; Rhizome; Serotonin; Stress, Psychological

The placebo effect has evolved from being considered a nuisance factor in clinical research to a hot topic of scientific investigation. New research findings show that a placebo has real psychobiological and biological effects that are attributable to the overall therapeutic context. Irritable bowel syndrome (IBS) is a functional disorder of the gastrointestinal tract that shows a significant placebo response of around 40–50% among different clinical trials.A positive patient-practitioner relationship can enhance the placebo effect in IBS patients.Emerging literature using functional brain imaging has started to document the neuronal changes associated with the placebo phenomenon in IBS patients, showing aberrant neural network during visceral placebo analgesia when compared to controls. Further promotion and integration of laboratory and clinical research are encouraged to advance the understanding of placebo mechanisms in IBS patients.

Topics: Abdominal Pain; Analgesics; Brain; Cholecystokinin; Clinical Trials as Topic; Colon; Drug Synergism; Gastrointestinal Agents; Humans; Irritable Bowel Syndrome; Magnetic Resonance Imaging; Meta-Analysis as Topic; Placebo Effect; Positron-Emission Tomography; Treatment Outcome

Post-infectious irritable bowel syndrome (PI-IBS) and functional dyspepsia (FD) have been described after both Campylobacter jejuni gastroenteritis and Giardia infection. After C. jejuni, there is increased rectal serotonin (5-HT)-containing EC cells and postprandial plasma 5-HT, while a pilot study suggested increased plasma cholecystokinin (CCK) after Giardia infection.. To determine changes in plasma and duodenal mucosal 5-HT and CCK in Giardia-induced PI-IBS.. A total of 32 patients previously infected with Giardia and 19 who had recovered fully (controls) completed symptom questionnaires. Endoscopic duodenal biopsies were obtained from all subjects and immunohistochemically stained for CCK, 5-HT and CgA containing entero-endocrine cells and mast cells. 5-HT content was also assessed. Twenty-one of 32 patients and 19 controls consumed a high-carbohydrate meal, while fasting and postprandial plasma CCK and 5-HIAA were measured.. Post-infectious irritable bowel syndrome patients had increased numbers of CCK cells (P = 0.02), but lower numbers of EC cells (P = 0.009). Plasma CCK did not differ significantly between the groups, but correlated significantly with postprandial dyspepsia scores (r = 0.5, P = 0.05). PI-IBS patients had significantly lower plasma 5-HIAA, before and after meal (P = 0.05) as well as more dyspepsia (P < 0.0001) compared with recovered subjects.. Post-infectious bowel dysfunction following Giardia infection is associated with increased duodenal mucosal CCK. Postprandial dyspeptic symptoms correlate better with CCK than measures of 5-HT metabolism.

Topics: Adult; Cholecystokinin; Dyspepsia; Giardiasis; Humans; Intestinal Mucosa; Irritable Bowel Syndrome; Middle Aged; Norway; Serotonin; Young Adult

General disturbances in gastrointestinal motility have been reported in patients with irritable bowel syndrome (IBS). The gastrointestinal tract hormones play an important role in regulating gastrointestinal motility.. To investigate a possible abnormality in the small intestinal endocrine cells of IBS patients.. Included in the study were 41 patients with irritable bowel syndrome according to Rome Criteria III and 42 healthy controls. Duodenal biopsies were obtained from both patients and controls during gastroscopy. The biopsies were immunostained by avidin-biotin-complex method for secretin, CCK, GIP, somatostatin, and serotonin cells. The cell densities were quantified by computerized image analysis.. The density of secretin- and CCK-immunoreactive cells in patients with IBS was significantly reduced. The reduction in secretin and CCK cells occurred only in IBS-diarrhea patients, but not in IBS-constipation subtype. Both GIP and somatostatin cell densities were reduced in the duodenum of IBS patients. There was no statistical difference between the subtypes of IBS patients, regarding secretin, CCK, GIP, or somatostatin cell densities. Serotonin cell density was not affected in patients with IBS.. The low densities of secretin and CCK cells in IBS-diarrhea patients may cause a functional pancreatic insufficiency as well as inadequate gall emptying, as these hormones stimulate pancreatic bicarbonate and enzyme secretion and CCK stimulates as well gall bladder contraction. Low densities of secretin, GIP, and somatostatin cells in IBS patients might result in a high secretion of gastric acid, as secretin, GIP, and somatostatin inhibit gastric acid secretion.

Topics: Adolescent; Adult; Cell Count; Cholecystokinin; Duodenum; Female; Gastroscopy; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Irritable Bowel Syndrome; Male; Middle Aged; Secretin; Serotonin; Somatostatin; Young Adult

Topics: Cholecystokinin; Emotions; Humans; Irritable Bowel Syndrome; Motilin; Music; Vascular Endothelial Growth Factor A

Based on better recent knowledge of the factors involved in triggering visceral hyperalgesia, the therapeutic approach to irritable bowel syndrome (IBS) treatment is changing. The classical approach targeting first bowel movement alterations or motility disorders using spasmolytic agents has to be replaced by visceral antinociceptive drugs. Several mediators and receptors involved in gut hyperalgesia have already been identified. Serotonin (5-HT), tachykinins, CCK, NGF, and other mediators are involved in experimental models of gut hyperalgesia, and related receptor antagonists have already been introduced in clinical trials. However, IBS is associated with mucosal immune stimulation, considered a microinflammatory state associated with increased density of immunocytes and mast cells, offering new targets. Altered mucosal barrier permeability with increased entry of toxins and bacteria is considered to be responsible for the mucosal microinflammation. Endogenous but predominantly luminal factors have been identified as factors responsible for such altered permeability. These clinical data have opened the door to promising future drugs able to prevent or blunt such permeability alteration, which therefore may constitute a pathophysiological treatment for IBS.

Topics: Animals; Cholecystokinin; Humans; Irritable Bowel Syndrome; Myosin-Light-Chain Kinase; Nerve Growth Factors; Parasympatholytics; Receptors, Opioid, kappa; Receptors, Tachykinin; Serine Proteinase Inhibitors; Serotonin Antagonists; Serotonin Receptor Agonists

Faults in a batch process model of the small intestine create the symptoms of all types of irritable bowel syndrome. The model has three sequential processing sections corresponding to the natural divisions of the intestine. It is governed by a brain controller that is divided into four sub-controllers, each with a unique neurotransmitter. Each section has a sub-controller to manage transport. Sensors in the walls of the intestine provide input and output goes to the muscles lining the walls of the intestine. The output controls the speed of the food soup, moves it in both directions, mixes it, controls absorption, and transfers it to the next section at the correct speed (slow). The fourth sub-controller manages the addition of chemicals. It obtains input from the first section of the process via the signalling hormone Cholecystokinin and sends output to the muscles that empty the gall bladder and pancreas. The correct amounts of bile salts and enzymes are then added to the first section. The sub-controllers produce output only when input is received. When output is missing the enteric nervous system applies a default condition. This default condition normally happens when no food is in the intestine. If food is in the intestine and a transport sub-controller fails to provide output then the default condition moves the food soup to the end of that section. The movement is in one direction only (forward), at a speed dependent on the amount and type of fibre present. Cereal, bean and vegetable fibre causes high speeds. This default high speed transport causes irritable bowel syndrome. A barrier is created when a section moving fast at the default speed, precedes a section controlled by a transport sub-controller. Then the sub-controller constricts the intestine to stop the fast flow. The barrier causes constipation, cramping, and bloating. Diarrhoea results when the section terminating the process moves at the fast default speed. Two problems can occur to prevent output from the sub-controllers. The first is a deficiency of one or more of the four neurotransmitters. The second is the destruction of sensors in the walls of the intestine by a toxic insult. A wide variety of symptoms can occur and their nature depends on which sub-controller (or combination of sub-controllers) is faulty, or which part(s) of the intestine are damaged.

Topics: Absorption; Adult; Bile Acids and Salts; Cholecystokinin; Humans; Intestinal Mucosa; Intestine, Small; Irritable Bowel Syndrome; Male; Middle Aged; Models, Biological; Models, Theoretical; Nervous System; Neurotransmitter Agents

Irritable bowel syndrome (IBS) is a functional bowel disorder which is characterized by abdominal pain and disturbed bowel habits. The pathophysiological mechanism is complex and still remains incompletely clear. Alterations at both the central and the peripheral level are thought to contribute to the symptoms of IBS, including psychosocial factors, visceral hypersensitivity and abnormal gastrointestinal motility and secretion. Several gut peptides contribute to the regulation of gastrointestinal function, but little is known about gut hormone secretion in IBS.. We evaluated the concentrations of cholecystokinin (CCK), vasoactive intestinal peptide (VIP), somatostatin, substance P, neuropeptide Y (NPY) in plasma and in sigmoid tissue in 40 patients with IBS and 15 age- and gender-matched controls by using radioimmunoassay.. IBS patients had higher plasma level of CCK (p < 0.01), and the level of CCK in the sigmoid was also increased compared with controls (p < 0.05). The levels of somatostatin and substance P in fasting plasma and in the sigmoid were not different between IBS patients and control subjects (p > 0.05), but the levels of VIP in sigmoid tissue or in plasma were higher in IBS patients than in control group (p < 0.01). The NPY levels in both plasma and the sigmoid were significantly lower in IBS patients than in controls (p < 0.05). Plasma NPY level in patients with IBS with diarrhea as a predominant bowel pattern was lower than in patients with IBS with constipation as a predominant bowel pattern.. IBS patients have increased levels of CCK and VIP and decreased NPY levels in fasting plasma and sigmoid tissue. These alterations of VIP, CCK and NPY may play a role in the pathogenesis of IBS.

Topics: Adult; Aged; Cholecystokinin; Female; Gastrointestinal Hormones; Humans; Irritable Bowel Syndrome; Male; Middle Aged; Neuropeptide Y; Somatostatin; Substance P; Vasoactive Intestinal Peptide