BACKGROUND: Irritable bowel syndrome (IBS) is one of the most common functional intestinal diseases, but its pathogenesis is still unknown. The present study aimed to screen the differentially expressed proteins in the mucosa of colon between IBS with diarrhea (IBS-D) patients and the healthy controls. METHODS: Forty-two IBS-D patients meeting the Rome III diagnostic criteria and 40 control subjects from July 2007 to June 2009 in Chinese PLA General Hospital were enrolled in the present study. We examined the protein expression profiles in mucosa of colon corresponding to IBS-D patients (n = 5) and controls (n = 5) using 2-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS). Secondly, Western blot and immunohistochemical analysis were carried out to validate the screened proteins in 27 IBS-D patients and 27 controls. Thirdly, high-performance liquid chromatography (HPLC) was further carried out to determine ATP concentration in the mucosa of colon between 10 IBS-D patients and 8 controls. Comparisons between 2 groups were performed by Student's t-test or Mann-Whitney U-test. RESULTS: Twelve differentially expressed proteins were screened out. The α-enolase (ENOA) in the sigmoid colon (0.917 ± 0.007 vs. 1.310 ± 0.100, t = 2.643, P = 0.017) and caecum (0.765 ± 0.060 vs. 1.212 ± 0.122, t = 2.225, P = 0.023), Isobutyryl-CoA dehydrogenase (ACAD8) in the sigmoid colon (1.127 ± 0.201 vs. 1.497 ± 0.392, t = 7.093, P = 0.008) of the IBS-D group were significantly lower while acetyl-CoA acetyltransferase (CT) in the caecum (2.453 ± 0.422 vs. 0.931 ± 0.652, t = 8.363, P = 0.015) and ATP synthase subunit d (ATP5H) in the sigmoid (0.843 ± 0.042 vs. 0.631 ± 0.042, t = 8.613,P = 0.007) of the IBS-D group was significantly higher, compared with the controls. The ATP concentration in the mucosa of the sigmoid colon in IBS-D group was significantly lower than that of control group (0.470 [0.180, 1.360] vs. 5.350 [2.230, 7.900], U = 55, P < 0.001). CONCLUSIONS Many proteins related to energy metabolism presented differential expression patterns in the mucosa of colon of the IBS-D patients. The abnormalities in energy metabolism may be involved in the pathogenesis of IBS which deserves more studies to elucidate.
Adenosine Triphosphate ; metabolism ; Adult ; Blotting, Western ; Colon ; metabolism ; pathology ; Diarrhea ; enzymology ; metabolism ; pathology ; Electrophoresis, Gel, Two-Dimensional ; Energy Metabolism ; genetics ; physiology ; Female ; Humans ; Immunohistochemistry ; Intestinal Mucosa ; enzymology ; metabolism ; pathology ; Irritable Bowel Syndrome ; enzymology ; metabolism ; pathology ; Male ; Mass Spectrometry ; Middle Aged ; Proteome ; metabolism

BACKGROUND/AIMS: Capsule endoscopy is a diagnostic method for evaluating the small bowel lumen and can detect undiagnosed lesions. The aim of this study was to evaluate the diagnostic yield and clinical impact of capsule endoscopy in patients with refractory diarrhea-predominant irritable bowel syndrome and functional abdominal pain. METHODS: This study involved a retrospective analysis of prospectively collected data, maintained in a database. Patients with refractory diarrhea-predominant irritable bowel syndrome and functional abdominal pain within the period of March 2012 to March 2014 were included. Capsule endoscopy was used to detect small bowel pathologies in both groups. RESULTS: Sixty-five patients (53.8% female) fulfilled the inclusion criteria and had a mean (±standard deviation) age of 50.9±15.9 years. Clinically significant lesions were detected via capsule endoscopy in 32.5% of the patients in the abdominal pain group and 54.5% of the patients in the diarrhea group. Overall, 48% of patients had small bowel pathologies detected during the capsule endoscopy study. Inflammatory lesions and villous atrophy were the most frequent lesions identified in 16.9% and 15.3% of patients in the abdominal pain and the diarrhea groups, respectively. CONCLUSIONS: Routine use of capsule endoscopy in patients with irritable bowel syndrome should not be recommended. However, in patients with refractory conditions, capsule endoscopy may identify abnormalities.
Abdominal Pain* ; Atrophy ; Capsule Endoscopy* ; Diarrhea ; Humans ; Irritable Bowel Syndrome* ; Methods ; Pathology ; Prospective Studies ; Retrospective Studies

Irritable bowel syndrome (IBS) is the most common disorder referred to gastroenterologists and is characterized by altered bowel habits, abdominal pain, and bloating. Visceral hypersensitivity (VH) is a multifactorial process that may occur within the peripheral or central nervous systems and plays a principal role in the etiology of IBS symptoms. The pharmacological studies on selective drugs based on targeting specific ligands can provide novel therapies for modulation of persistent visceral hyperalgesia. The current paper reviews the cellular and molecular mechanisms underlying therapeutic targeting for providing future drugs to protect or treat visceroperception and pain sensitization in IBS patients. There are a wide range of mediators and receptors participating in visceral pain perception amongst which substances targeting afferent receptors are attractive sources of novel drugs. Novel therapeutic targets for the management of VH include compounds which alter gut-brain pathways and local neuroimmune pathways. Molecular mediators and receptors participating in pain perception and visceroperception include histamine-1 receptors, serotonin (5-hydrodytryptamine) receptors, transient receptor potential vanilloid type I, tachykinins ligands, opioid receptors, voltage-gated channels, tyrosine receptor kinase receptors, protease-activated receptors, adrenergic system ligands, cannabinoid receptors, sex hormones, and glutamate receptors which are discussed in the current review. Moreover, several plant-derived natural compounds with potential to alleviate VH in IBS have been highlighted. VH has an important role in the pathology and severity of complications in IBS. Therefore, managing VH can remarkably modulate the symptoms of IBS. More preclinical and clinical investigations are needed to provide efficacious and targeted medicines for the management of VH.
Abdominal Pain ; Central Nervous System ; Gonadal Steroid Hormones ; Humans ; Hyperalgesia ; Hypersensitivity* ; Irritable Bowel Syndrome* ; Ligands ; Pain Perception ; Pathology ; Phosphotransferases ; Receptors, Adrenergic ; Receptors, Cannabinoid ; Receptors, Glutamate ; Receptors, Opioid ; Receptors, Proteinase-Activated ; Receptors, Serotonin ; Tachykinins ; Tyrosine ; Visceral Pain

Bile acid diarrhea (BAD) is usually seen in patients with ileal Crohn's disease or ileal resection. However, 25% to 50% of patients with functional diarrhea or diarrhea-predominant irritable bowel syndrome (IBS-D) also have evidence of BAD. It is estimated that 1% of the population may have BAD. The causes of BAD include a deficiency in fibroblast growth factor 19 (FGF-19), a hormone produced in enterocytes that regulates hepatic bile acid (BA) synthesis. Other potential causes include genetic variations that affect the proteins involved in BA enterohepatic circulation and synthesis or in the TGR5 receptor that mediates the actions of BA in colonic secretion and motility. BAs enhance mucosal permeability, induce water and electrolyte secretion, and accelerate colonic transit partly by stimulating propulsive high-amplitude colonic contractions. There is an increased proportion of primary BAs in the stool of patients with IBS-D, and some changes in the fecal microbiome have been described. There are several methods of diagnosing BAD, such as 75selenium homotaurocholic acid test retention, serum C4, FGF-19, and fecal BA measurement; presently, therapeutic trials with BA sequestrants are most commonly used for diagnosis. Management involves the use of BA sequestrants including cholestyramine, colestipol, and colesevelam. FXR agonists such as obeticholic acid constitute a promising new approach to treating BAD.
Anticholesteremic Agents/therapeutic use ; Bile Acids and Salts/*physiology ; Crohn Disease/complications ; Diarrhea/*etiology/pathology/therapy ; Feces/chemistry ; Fibroblast Growth Factors/deficiency ; Gastrointestinal Microbiome ; Humans ; Irritable Bowel Syndrome/complications

OBJECTIVETo observe the effect of Tongxie Yaofang (TY) on the number of mast cells (MCs) and the expression of cytokines in rats with visceral hypersensitivity, and to explore roles of TY in treating visceral hypersensitivity and its possible mechanism.

METHODSTotally 30 male adult Sprague Dawley (SD) rats were randomly divided into the blank control group, the model group, and the TY treatment group, 10 in each group. The irritable bowel syndrome (IBS) rat model was established by combining colorectal distention with restraint stress in the TY treatment group and the model group. The visceral hypersensitivity was assessed by abdominal withdrawal reflex (AWR). From the 2nd day of successful modeling, rats in the treatment group were admiministered with TY at the daily dose of 4 g/kg for 4 successive weeks. Equal volume of normal saline was given to rats in the model group for 4 successive weeks. No treatment was given to rats in the blank control group. Four weeks later the number of MCs was counted by using toluidine blue staining. The expression of interleukin-4 (IL-4) and interleukin-9 (IL-9) both in colonic mucosa and serum were measured by enzyme linked immunosorbent assay (ELISA), and the expression of protease-activated receptor type 2 (PAR-2) was detected by Western blot.

RESULTSCompared with the blank control group, the visceral sensitivity was significantly elevated, the number of MCs in the ileocecal junction increased, and the expression of IL-4, IL-9, and PAR-2 in serum and the colonic mucosa significantly increased (P < 0.05). Compared with the model group, the visceral sensitivity significantly decreased, the number of MCs reduced, and the expression of PAR-2 in the colonic mucosa significantly reduced (all P < 0.05), and the expression of IL-4 in colonic mucosa and IL-9 in serum were obviously reduced in the TY treatment group (P < 0.05).

CONCLUSIONTY might improve the visceral hypersensitivity by acting on MCs related cytokines and reducing degranulation of MCs.

Animals ; Cytokines ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Intestines ; drug effects ; metabolism ; pathology ; Irritable Bowel Syndrome ; drug therapy ; metabolism ; pathology ; Male ; Mast Cells ; drug effects ; Rats ; Rats, Sprague-Dawley

Irritable bowel syndrome (IBS) is one of the most prevalent functional gastrointestinal disorders. It is a multifactorial disorder with its pathogenesis attributed to abnormal gastrointestinal motility, low-grade inflammation, visceral hypersensitivity, communication in the gut-brain axis, and so on. Traditionally, IBS has been treated with diet and lifestyle modification, fiber supplementation, psychological therapy, and pharmacological treatment. Carbohydrates are intermingled with a wide range of regularly consumed food including grains such as rye and wheat, vegetables, fruits, and legumes. Short-chain carbohydrates that are poorly absorbed exert osmotic effects in the intestinal lumen increasing its water volume, and are rapidly fermented by bacteria with consequent gas production. These effects may be the basis for the induction of most of the gastrointestinal symptoms. This has led to the use of lactose-free diets in those with lactose intolerance and of fructose-reduced diets for fructose malabsorption. As all poorly absorbed short-chain carbohydrates have similar and additive effects in the intestine, a concept has been developed to regard them collectively as FODMAPs (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) and to evaluate a dietary approach that restricts them all. Based on the observational and comparative studies, and randomized-controlled trials, FODMAPs have been shown to trigger gastrointestinal symptoms in patients with IBS. Food choice via the low FODMAPs and potentially other dietary strategies is now a realistic and efficacious therapeutic approach for managing symptoms of IBS.
*Diet, Carbohydrate-Restricted ; Dietary Supplements ; Humans ; Hypersensitivity/complications ; Inflammation/complications ; Intestines/pathology ; Irritable Bowel Syndrome/complications/*diagnosis/diet therapy ; Malabsorption Syndromes/complications ; Monosaccharides/metabolism ; Oligosaccharides/metabolism

Functional gastrointestinal (GI) disorders are common in the general population. Based on the Rome III classification, these disorders are mutually exclusive disorders keeping the homogeneity of each functional GI disorder in research area. In contrast, many population and clinical studies have reported a considerably high rate of overlap between functional GI disorders. The overlap of functional GI disorders over other intestinal diseases might simply occur by chance due to a highly prevalent disorder. Moreover, functional GI disorders is considered a chronic stable disorder that may wax and wane for several years. However, a recent study about the natural history of functional GI disorders showed substantial transition among functional GI disorders over time. The natural history of functional GI disorders with overlapping other functional GI disorders are still in infancy and better understanding of these will be important in determining the efficacy of future therapeutic interventions.
Dyspepsia/epidemiology/pathology ; Esophageal and Gastric Varices/epidemiology/pathology ; Gastrointestinal Diseases/epidemiology/*pathology ; Humans ; Irritable Bowel Syndrome/epidemiology/pathology ; Prevalence

Previous reviews have highlighted complementary and alternative medicine therapies that are used to treat irritable bowel syndrome (IBS) based on published clinical trial data. Here the author describes and comments on a number of potentially relevant factors that have been commonly emphasized by practitioners who treat IBS and patients who have the disease. They include gluten and other food allergies, the candida syndrome and biofilm, interference fields and post-infectious IBS, as well as mind-body factors.
Food Hypersensitivity ; complications ; immunology ; Glutens ; immunology ; Humans ; Integrative Medicine ; Irritable Bowel Syndrome ; complications ; microbiology ; pathology ; therapy ; Mind-Body Therapies ; Wound Healing

BACKGROUND/AIMS: The endoscopic findings and clinical relevance of portal hypertensive colopathy are not well described in Korea. We aimed to do a retrospective study of mucosal changes in the colon of patients with liver cirrhosis and to find their association with clinical characteristics. METHODS: We reviewed the clinical data and endoscopic findings of 48 patients with liver cirrhosis and 48 patients, matched for age and sex, with irritable bowel disease (IBS) who underwent colonoscopy over a 5 year span. RESULTS: Patients with liver cirrhosis were more likely to have colitis-like lesions and vascular abnormalities than IBS patients. Low platelet count (p=0.005) and severe esophageal varices (p=0.011) were associated with portal hypertensive colopathy, whereas the etiologies and severity of cirrhosis were not associated with these findings. CONCLUSIONS: Portal hypertensive colopathy can be defined with colitis-like lesions or vascular lesions. These lesions are more frequently present in patients with more severe esophageal varices and thrombocytopenia.
Adult ; Aged ; Colonoscopy ; Esophageal and Gastric Varices/etiology ; Female ; Humans ; Hypertension, Portal/complications/*pathology ; Intestinal Mucosa/pathology ; Irritable Bowel Syndrome/complications/*pathology ; Liver Cirrhosis/complications/*pathology ; Male ; Middle Aged ; Platelet Count ; Retrospective Studies ; Severity of Illness Index ; Thrombocytopenia/etiology

Alverine citrate is one of the most commonly used antispasmodic drugs for patients with irritable bowel syndrome. Alverine-citrate-induced hepatotoxicity is extremely rare, with only a few cases having been reported worldwide. We present a case of a 75-year-old female patient who experienced complicated jaundice and abdominal discomfort after taking alverine citrate. Other causes of hepatitis were ruled out and the results of the liver function test returned to normal after ceasing the drug. This is the first case report in Korea of alverine-citrate-induced hepatotoxicity.
Acute Disease ; Aged ; Citrates/*adverse effects/therapeutic use ; Drug-Induced Liver Injury/*diagnosis/etiology/pathology ; Female ; Humans ; Irritable Bowel Syndrome/drug therapy ; Liver Function Tests ; Parasympatholytics/*adverse effects/therapeutic use ; Propylamines/*adverse effects/therapeutic use ; Tomography, X-Ray Computed