Qiao Yu

Cognitive–behavioral therapy for irritable bowel syndrome: A meta-analysis

OBJECTIVE To establish whether cognitive behavioral therapy (CBT) improves the bowel symptoms, quality of life (QOL) and psychological states of irritable bowel syndrome (IBS) patients. METHODS Randomized controlled trials (RCTs) of CBT for adult patients with IBS were searched by using PubMed, Scopus and Web of Science. The standardized mean difference (SMD) with 95% confidence intervals (CIs) of the evidence-based outcome measures of the IBS bowel symptoms, QOL and psychological states at post-treatment and follow-up was calculated. Prespecified subgroup analysis was performed. RESULTS Eighteen RCTs satisfied our inclusion criteria. In the subgroup analyses, CBT was more effective in reducing IBS bowel symptoms, QOL and psychological states than waiting list controls at the end of the intervention and short-term follow-up. When compared with controls of basic support and medical treatment, the effect sizes were found to favor CBT for the improvement of IBS bowel symptoms at post-treatment and short-term follow-up, but CBT was not superior to controls in improving QOL and psychological states. When comparing CBT with other psychological controls, the effect sizes were almost non-significant. CONCLUSIONS For IBS patients, CBT was superior to waiting list, basic support or medical treatment at the end of treatment but not superior to other psychological treatments. The meta-analysis might be limited by the heterogeneities and small sample sizes of the included studies.

Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease.

BackgroundThe IL23/Th17 pathway is essential for the onset of inflammatory bowel disease (IBD), yet the specific mechanism by which this pathway initiates the disease remains unknown. In this study, we identify the mechanisms that mediate cross-talk between the IL23 pathway and the intestinal barrier in IBD.ResultsThe downstream targets of the IL23 pathway were identified by RNA array profiling and confirmed by immunohistochemical staining. The role of miRNAs that interact with IL23 was explored in mice with TNBS-induced colitis. Claudin-8 (CLDN8), a multigene family protein that constitutes the backbone of tight junctions, was identified as a novel target of IL23 in IBD. CLDN8 was significantly downregulated in IBD patients with inflamed colonic mucosa, and in trinitrobenzene sulphonic acid (TNBS) induced colitis in mice. Therapeutic treatment of colitis in mice using an IL23 antibody restored CLDN8 abundance, in parallel with recovery from colitis. In addition, we identify miR-223 as a novel mediator of the crosstalk between the IL23 signal pathway and CLDN8 in the development of IBD. MiR-223 was upregulated in IBD, and its activity was regulated through the IL23 pathway. Antagomir inhibition of miR-223 reactivated CLDN8 and improved a number of signs associated with TNBS-induced colitis in mice.ConclusionsOur study characterizes a new mechanistic pathway in IBD, in which miR-223 interacts with the IL23 pathway by targeting CLDN8. Strategies designed to disrupt this interaction may provide novel therapeutic agents for the management of IBD.

Circulating MicroRNA223 is a New Biomarker for Inflammatory Bowel Disease

Abstract Endoscopy is an important tool in screening and monitoring inflammatory bowel disease (IBD); however, it is invasive, costly, and associated with risks to the patients. Recently, circulating microRNAs (miRNAs) have emerged as promising noninvasive biomarkers. We proposed that the expression of serum microRNA223 (miR-223) could be a biomarker for IBD. Studies were conducted using serum samples from 100 patients with IBD (50 with Crohns disease [CD] and 50 with ulcerative colitis [UC]) and 50 healthy controls. The expression of serum miR-223 was measured by quantitative reverse transcription-polymerase chain reaction. The clinical disease activity was assessed by measurement of the Crohns disease activity index for CD and the Mayo score for UC. Endoscopies were performed and graded according to the simple endoscopic score for CD and the ulcerative colitis endoscopic index of severity scores for UC. Blood samples for the measurement of high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate (ESR) were taken within 1 week before or after endoscopy. Serum miR-223 expression increased 2.2 times in patients with CD and 2.8 times in patients with UC compared with the control group. Most importantly, the level of serum miR-223 was correlated with several indicators of disease activity both in CD and UC. Serum miR-223 demonstrated a higher Spearman r value than ESR and hs-CRP in detecting the disease activity of patients with IBD. Serum miR-223 might be a promising biomarker for monitoring disease activity in IBD patients.

E3 Ubiquitin ligase RNF183 Is a Novel Regulator in Inflammatory Bowel Disease.

BACKGROUND AND AIMS Specific members of the RING finger [RNF] protein family serve as E3 ubiquitin ligases and play important roles in the regulation of inflammation. However, their roles in the pathogenesis of inflammatory bowel disease [IBD] have not been explored. METHODS Genomic microarray of inflamed colon samples from Crohns disease [CD] patients was performed to identify potential up-regulated genes. Expression of the identified highly up-regulated RNF183 gene was subsequently examined by quantitative reverse transcription polymerase chain reaction [qRT-PCR], western blotting and immunohistochemistry of the intestinal tissues of IBD patients and the colons of trinitrobenzene sulphonic acid [TNBS]-induced colitic mice. RNF183-mediated interaction with the NF-κB pathway and ubiquitination of IκBα were examined by siRNA, plasmid transfection, and immunoprecipitation. The miRNA predicted to target RNF183 was explored and its role in the RNF183/ NF-κB pathway was investigated. RESULTS RNF183 was up-regulated in intestinal epithelial cells in IBD patients and in colitic mice. RNF183 promoted intestinal inflammation via the activation of the NF-κB pathway by increasing the ubiquitination and degradation of IκBα. Computational analysis identified putative binding of miR-7 to RNF183. Transfection of intestinal cells with a miR-7 mimic or inhibitor confirmed its negative regulatory effect on RNF183 expression and ubiquitination of IκBα. miR-7 was down-regulated in inflamed colon tissues of IBD patients and colitic mice. CONCLUSIONS RNF183, which is negatively regulated by miR-7, is a novel regulator promoting intestinal inflammation by increasing the ubiquitination and degradation of IκBα, thereby inducing NF-κB activation. The interaction between RNF183-mediated ubiquitination and miRNA may be an important novel epigenetic mechanism in the pathogenesis of IBD.

Enterohepatic Helicobacter Species as a Potential Causative Factor in Inflammatory Bowel Disease: A Meta-Analysis.

AbstractThe Helicobacter species in the gut microbiota comprise Helicobacter pylori (H pylori) and enterohepatic Helicobacter species (EHS), which can colonize the intestinal mucosa. However, it is unclear whether EHS are associated with inflammatory bowel disease (IBD). Therefore, we conducted this meta-analysis to examine the association between EHS and IBD.PubMed, Scopus, Cochrane Library, and Web of Science databases, as well as abstracts from conference proceedings were searched to identify studies that used polymerase chain reaction to detect Helicobacter species in intestinal samples from patients with IBD.After screening, we carefully reviewed 20 of the 2955 identified studies, and performed a meta-analysis of the findings from 14 studies (11 adult studies and 3 pediatric studies) using STATA v12.0. These studies evaluated 1407 individuals, including 433 patients with Crohns disease, 306 patients with ulcerative colitis, and 668 controls. The prevalence of Helicobacter species was higher among the patients with IBD, compared to that among the controls, which corresponded to a pooled risk ratio (RR) of 1.59 (95% confidence interval [CI]: 1.12–2.27). The RRs for adult and pediatric patients with IBD were 1.61 (95% CI: 1.03–2.52) and 1.76 (95% CI: 1.17–2.64), respectively. Compared to the controls, the patients with IBD tended to have a higher prevalence of EHS in the intestinal mucosa (RR: 2.01, 95% CI: 1.36–2.98), although the prevalence of H pylori was not significantly higher (RR: 1.22, 95% CI: 0.77–1.95). Compared to the controls, the RRs for EHS in patients with Crohns disease and ulcerative colitis were 1.72 (95% CI: 1.20–2.47) and 3.27 (95% CI: 0.93–11.44), respectively.It appears that EHS was associated with IBD, while intestinal H pylori infection was not significantly associated with IBD. Further studies are needed to determine the involvement of EHS in the microbiological etiology of IBD.

The ‐A2518G polymorphism in the MCP‐1 gene and inflammatory bowel disease risk: A meta‐analysis

The monocyte chemoattractant protein‐1 (MCP‐1) ‐A2518G gene polymorphism has been found to be involved in the susceptibility to inflammatory bowel disease (IBD); however, the results of existing studies are controversial. The aim of this meta‐analysis was to assess the relationship between the MCP‐1 ‐A2518G polymorphism and the risk of IBD.

Increased small intestinal permeability and RNA expression profiles of mucosa from terminal ileum in patients with diarrhoea-predominant irritable bowel syndrome.

BACKGROUND Altered intestinal permeability in diarrhoea-predominant irritable bowel syndrome (IBS-D) has been reported in some studies. AIMS The study aimed to investigate the altered intestinal permeability and its associated clinical characteristics and RNA expression profiles in IBS-D. METHODS We stratified IBS-D patients into two groups according to the P95 value of the permeability in controls. The clinical characteristics of the two groups were evaluated, and two biopsy cases from each of the two groups were selected for the RNA-seq analysis. RESULTS IBS-D patients had a significant increase in the small intestinal permeability compared with controls [0.0245 (0.0229) median (interquartile range)] versus 0.0156 (0.0098), P=0.010), but no significant difference was found in the colonic permeability [23.286 (10.470) versus 21.650 (6.650), P=0.574]. The IBS-D patients with increased small intestinal permeability had worse psychological effects (P=0.027) and quality of life (P=0.044). Analysis of RNA-seq data revealed 185 genes differentially expressed, many of which were related to mucosal inflammation and immunity. CONCLUSIONS Small intestinal permeability, but not colonic permeability, is increased in IBS-D patients. IBS-D patients with increased small intestinal permeability tend to be more severely impaired in terms of psychological effects and quality of life, and analysis of RNA-seq data reveals that increased small intestinal permeability is related to mucosal inflammation and immunity.

TNFAIP6 is a potential biomarker of disease activity in inflammatory bowel disease.

AIM Ideal biomarkers are needed for evaluating the activity of inflammatory bowel disease (IBD). We aimed to investigate the value of TNFAIP6 as a biomarker. MATERIALS & METHODS Inflamed colonic samples and serum samples were collected from patients with Crohns disease (CD), patients with ulcerative colitis (UC), and normal controls. SPSS 18.0 was used for statistical analysis. RESULTS Serum TNFAIP6 was higher in IBD patients than in normal controls and correlated with the inflammatory indicators. Compared with active patients, TNFAIP6 was decreased in both CD and UC patients in remission. Furthermore, TNFAIP6 concentrations consistent with TNF-α level, correlated well with disease location and extent of both CD and UC. CONCLUSION Serum TNFAIP6 may be a promising biomarker for evaluating the disease activity of IBD, demonstrating the diagnostic value in disease location differentiation.

The role of ABO blood groups in Crohn's disease and in monitoring response to infliximab treatment.

BACKGROUND The variation in ABO blood groups is reported to be associated with multiple diseases. Infliximab (IFX) has been widely used in the treatment of Crohns disease (CD). We aim to investigate the distribution of ABO blood groups in Chinese patients with CD and to explore its impact on response to IFX. MATERIALS AND METHODS Patients with CD were consecutively recruited to the study between 2007 and 2014. CD patients receiving IFX therapy were followed for at least two years. RESULTS In 293 patients with CD, most patients (40.6%) had blood type O (119/293). The odds ratio (OR) of CD in blood type O patients was 1.06 (95%CI: 0.6-1.86; p=0.84) compared to all other blood types. Among those CD patients, 107 patients received IFX treatment. One year after the first course of IFX, a significant association was found between the overall ABO system and outcomes of IFX treatment (p<0.001). CD patients with blood type AB (OR=4.42, 95% CI: 1.04-18.76; p=0.044) were more likely to achieve mucosal healing, while CD patients with blood type A had a high risk of losing response (OR=0.38, 95% CI: 0.15-0.96; p=0.040). DISCUSSION ABO blood groups are not associated with prevalence of CD. Patients with blood type AB had a better response to IFX while those with blood type A appeared to have a risk of losing response to IFX.