Tao Bai

Mast Cell-dependent Mesenteric Afferent Activation by Mucosal Supernatant From Different Bowel Segments of Guinea Pigs With Post-infectious Irritable Bowel Syndrome

Background/Aims Mesenteric afferent nerves (MANs) play a pivotal role in the visceral-nociceptive perception. Inappropriate activation of MANs may be involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. We assessed the effects of mucosal mediators from different bowel segments of guinea pigs with PI-IBS on MAN firing and the role of mast cells. Methods PI-IBS was induced in guinea pigs by Trichinella spiralis infection. Inflammation in terminal ileum, proximal and distal colon was scored with hematoxylin-eosin staining, and mast cell infiltration was assessed with immunofluorescence. We determined the effects of supernatant extracted from the mucosa of different bowel segments of PI-IBS on MANs activity, and assessed the role of mast cells in this process. Results Eight weeks after infection, intestinal inflammation resolved, whereas mast cell numbers increased significantly in terminal ileum and proximal colon (P < 0.05) compared with findings in controls. Mucosal supernatant from different bowel segments of PI-IBS models, but not from controls, significantly enhanced the frequency of MAN firing (terminal ileum 41.01 ± 7.60 Hz vs. 26.55 ± 0.67 Hz, P = 0.001; proximal colon 45.90 ± 11.20 Hz vs. 30.88 ± 6.92 Hz, P = 0.002; distal colon 48.25 ± 9.70 Hz vs. 29.47 ± 6.13 Hz, P < 0.001). In addition, the excitatory effects were inhibited by mast cell stabilizer Nasmil (terminal ileum, 32.71 ± 2.52 Hz, P = 0.030; proximal colon, 30.94 ± 4.44 Hz, P = 0.002; distal colon, 27.15 ± 5.83 Hz, P < 0.001). Conclusions Supernatant from the intestinal mucosa of different bowel segments of PI-IBS models markedly enhanced the MAN firing in a mast cell-dependent manner, indicating that mast cell-mediated MAN activation plays an important role in the pathogenesis of PI-IBS.

Comparison of the Rome IV and Rome III criteria for IBS diagnosis: A cross-sectional survey

The aims of this study were to investigate the proportion of clinical irritable bowel syndrome (IBS) at a tertiary hospital in China, to compare the Rome III and Rome IV criteria with regard to IBS diagnosis, to describe the agreement between the Rome III and Rome IV criteria, and to identify differences between Rome IV‐positive and ‐negative IBS patients.

Stress induces more serious barrier dysfunction in follicle-associated epithelium than villus epithelium involving mast cells and protease-activated receptor-2

Psychological stress has been associated with intestinal epithelial hyperpermeability, the basic process in various functional and organic bowel diseases. In the present study, we aimed to clarify the differences and underlining mechanisms in stress-induced barrier disruption in functionally and structurally distinct epitheliums, including the villus epithelium (VE) and follicle-associated epithelium (FAE), a specialized epithelium overlaid the domes of Peyer’s lymphoid follicles. Employing an Ussing Chamber system, the epithelial permeability was assessed in rats following water avoidance stress (WAS) in vivo and in mucosa tissues exposed to corticotropin-releasing factor (CRF) ex vivo. Decreased transepithelial resistance (TER) and increased paracellular and transcellular macromolecular permeability in colon, ileal VE and FAE had been observed in WAS rats and in CRF-exposed mucosa. Especially, the barrier dysfunction was more serious in the FAE. Moreover, WAS upregulated the expression of mast cell tryptase and protease-activated receptor-2 (PAR2), which positively correlated with epithelial conductance. Mast cell stabilizer cromolyn sodium obviously alleviated the barrier disruption induced by WAS in vivo and CRF in vitro. Serine protease inhibitor aprotinin and FUT-175, and selective PAR2 antagonist ENMD-1068 effectively inhibited the CRF-induced FAE hyperpermeability. Altogether, it concluded that the FAE was more susceptible to stress, and the mast cells and PAR2 signaling played crucial roles in this process.

Inhibition effect of Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis and their related products on human colonic smooth muscle in vitro

Objective To investigate the effects of four strains, generally used in clinic, including Bifidobacterium longum, Lactobacillus acidophilus, Streptococcus thermophilus and Enterococcus faecalis, and their related products on human colonic smooth muscle in vitro. Methods Human colonic circular muscle strips obtained from disease-free margins of resected segments from 25 patients with colorectal cancer were isometrically examined in a constant-temperature organ bath and exposed to different concentrations of living bacteria, sonicated cell fractions and cell-free supernatant (CFS). The area under the curve (AUC) representing the contractility of smooth muscle strips was calculated. Results (1) The four living probiotics inhibited the contractility of human colonic muscle strips only at high concentration (1010 CFUs/mL, all P<0.05). (2) The sonicated cell fractions from the four probiotics obviously inhibited human colonic smooth muscle strips in a dose-dependent manner (P<0.01). (3) The CFS from the four probiotics also inhibited colonic smooth muscle strips in a dose-dependent manner (all P<0.05). (4) The inhibition effect of CFS from Streptococcus thermophilus and Enterococcus faecalis decreased obviously when pretreated with NG-nitro-L-arginine (L-NNA, 10−5 mol/L) (P<0.05), but not the Bifidobacterium longum and Lactobacillus acidophilus (P>0.05). Conclusion Four common probiotics related products, including the sonicated cell fractions and the CFS, obviously inhibited human colonic smooth muscles strips contraction in a dose-dependent manner. Only high concentration living probiotics (1010 CFUs/mL) can inhibit the colonic smooth muscles strips contraction. The NO pathway may be partly involved in the inhibitory effect of CFS from Streptococcus thermophilus and Enterococcus faecalis.

Piezo2: A Candidate Biomarker for Visceral Hypersensitivity in Irritable Bowel Syndrome?

Background/Aims Currently, there exists no biomarker for visceral hypersensitivity in irritable bowel syndrome (IBS). Piezo proteins have been proven to play an important role in the mechanical stimulation to induce visceral pain in other tissues and may also be a biomarker candidate. The aim of this study was to test the expressions of Piezo1 and Piezo2 proteins in the intestinal epithelial cells from different intestinal segments and to explore the correlation between Piezo proteins expression and visceral pain threshold. Methods Post-infectious IBS was induced in mice via a Trichinella spiralis infection. Visceral sensitivity was measured with abdominal withdrawal reflex to colorectal distention. Inflammation in the small intestine and colon was scored with H&E staining. Expression location of Piezo proteins was confirmed by immunohistochemistry. Abundance of Piezo proteins were measured with real-time reverse transcriptase polymerase chain reaction. Results Piezo1 and Piezo2 proteins were expressed in the intestinal epithelial cells. The expression levels of Piezo1 and Piezo2 were abundant in the colon than the small intestine (P < 0.001 for Piezo1, P = 0.003 for Piezo2). Expression of Piezo2 in the colon significantly correlated to the visceral sensitivity (r = −0.718, P = 0.001) rather than the mucosal inflammation. Conclusion Piezo2 is a candidate biomarker for visceral hypersensitivity in IBS.

Health-related quality of life in gastroesophageal reflux patients with noncardiac chest pain: Emphasis on the role of psychological distress.

AIM To investigate the effects of depression and anxiety on health-related quality of life (QoL) in gastroesophageal reflux disease (GERD) patients and those suffering from cardiac (CCP) and noncardiac (NCCP) chest pain in Wuhan, China. METHODS In this cross-sectional study, a total of 358 consecutive patients with GERD were enrolled in Wuhan, China, of which 176 subjects had complaints of chest pain. Those with chest pain underwent coronary angiography and were divided into a CCP group (52 cases) and NCCP group (124 cases). Validated GERD questionnaires were completed, and the 36-item Short-Form Health Survey and Hospital Anxiety/Depression Scale were used for evaluation of QoL and psychological symptoms, respectively. RESULTS There were similar ratios and levels of depression and anxiety in GERD with NCCP and CCP. However, the QoL was obviously lower in GERD with CCP than NCCP (48.34 ± 17.68 vs 60.21 ± 20.27, P < 0.01). In the GERD-NCCP group, rather than the GERD-CCP group, the physical and mental QoL were much poorer in subjects with depression and/or anxiety than those without anxiety or depression. Anxiety and depression had strong negative correlations with both physical and mental health in GERD-NCCP (all P < 0.01), but only a weak relationship with mental components of QoL in GERD-CCP. CONCLUSION High levels of anxiety and depression may be more related to the poorer QoL in GERD patients with NCCP than those with CCP. This highlights the importance of evaluation and management of psychological impact for improving QoL in GERD-NCCP patients.

Diagnostic performance of confocal laser endomicroscopy for atrophy and gastric intestinal metaplasia: A meta-analysis.

To systematically evaluate the diagnostic efficacy of confocal laser endomicroscopy (CLE) for gastric atrophy (GA) and gastric intestinal metaplasia (GIM).

Psychological distress as a crucial determinant for quality of life in patients with noncardiac chest pain in Central China: A cross-sectional study

AbstractIncreased psychiatric comorbidity, predominantly anxiety and depressive symptoms, and lower quality of life (QoL) are associated with noncardiac chest pain (NCCP). We aimed to investigate the roles of anxiety and depression in the impaired QoL of NCCP patients in Central China.In this hospital-based cross-sectional study, 200 consecutive patients who complained of chest pain with normal coronary angiography were enrolled in the Department of Cardiology and Gastroenterology, Union Hospital, Wuhan, China. Meanwhile, 100 healthy controls, with age and sex-matched, were recruited. Upper gastrointestinal endoscopy was undergone and a standardized symptom questionnaire was completed in NCCP patients. Levels of anxiety and depression and QoL were assessed using locally translated and validated versions of the Hospital Anxiety and Depression Scale (HADS) and the 36-item Short Form Health Survey (SF-36), respectively.The NCCP patients had poorer physical and mental QoL compared with the controls, and nearly half of them had anxiety (49.7%) and depression (40.1%). Those with anxiety and/or depression had lower physical (PCS) and mental (MCS) component summary score compared with those without anxiety and depression. Increased levels of anxiety and depression were associated with lower PCS (r = −0.469 and −0.523 respectively, P < 0.001) and MCS (r = −0.474 and −0.440, respectively, P < 0.001). The chest pain, heartburn, and anxiety were independent factors influence on both PCS and MCS. Moreover, psychological distress, besides directly acting on the QoL, may also mediate indirectly effects of physical symptoms on both the physical and mental QoL.We demonstrated that anxiety and depression are important determinants for the QoL of NCCP patients. Therefore, interventions should emphasize on identifying and treating the psychological impact in NCCP.

Effects of Buscopan on human gastrointestinal smooth muscle activity in an ex vivo model: Are there any differences for various sections?

Hyoscine butylbromide (Buscopan ®) is clinically used as an anticholinergic antispasmodic for the treatment of abdominal cramping or visceral pain associated with cramps. However, the spasmolytic efficacy on contractile activity of human gastrointestinal smooth muscle from various sections remains unclear. We aimed to investigate the potentially selective actions of Buscopan on different bowel segments, as well as muscular layers and contractile states. Human smooth muscle tissues of the esophagus, gastric corpus and antrum, jejunum, ileum and colon were obtained. Isometric measurements of circular and longitudinal muscle strips were performed to determine effects of Buscopan on spontaneous activity and induced-contractions by 30mM KCl, 10μM bethanechol and electrical field stimulation (EFS). Buscopan concentration-dependently (10(-9)-10(-5)M) inhibited smooth muscle activity, particularly in spasticity evoked by bethanechol and EFS but not high K(+). The inhibiting effects were mainly responsible for the antagonism on muscarinic M2 and M3 receptors (IC50 values: 3.1×10(-5)M vs. 0.9×10(-5)M). The sensitivity toward Buscopan revealed a tendency of increasing from the esophagus, gastric corpus and antrum to the colon, jejunum and ileum. There was a reversed gradient of mRNA and protein expression of muscarinic M2 and M3 receptors from the blocking effects of Buscopan, which could be ascribed to the fact that a higher concentration of Buscopan was needed to antagonize the spastic contraction to reach the equipotent inhibitory rate in the region with higher muscarinic receptor activity. The findings of different inhibitory effectiveness on various parts of the gastrointestinal tract provide a potential guideline for the clinical application.

Sustained pain hypersensitivity in the stressed colon: Role of mast cell-derived nerve growth factor-mediated enteric synaptic plasticity

Sustained pain hypersensitivity is the hallmark of stressed colon which could be partially explained by central sensitization with synaptic plasticity, the key mechanism of memory. We previously identified that synaptic plasticity of enteric nerve system (ENS) contributed to peripheral pain maintaining in the gut. However, the mechanisms of enteric “memory” formation remain elusive.