Background/Aims: Irritable bowel syndrome with diarrhoea (IBS-D) is a chronic, functional bowel disorder characterized by abdominal pain or diarrhoea and altered bowel habits, which correlate with intestinal hyperpermeability. MicroRNAs (miRNAs) are involved in regulating intestinal permeability in IBS-D. However, the role of miRNAs in regulating intestinal permeability and protecting the epithelial barrier remains unclear. Our goals were to (i) identify differential expression of miRNAs and their targets in the distal colon of IBS-D rats; (ii) verify in vitro whether occludin (OCLN) and zonula occludens 1 (ZO1/TJP1) were direct targets of miR-144 and were down-regulated in IBS-D rats; and (iii) determine whether down-regulation of miR-144 in vitro could reverse the pathological hallmarks of intestinal hyperpermeability via targeting OCLN and ZO1. Methods: The IBS-D rat model was established using 4% acetic acid and evaluated by haematoxylin-eosin (HE) staining. The distal colon was obtained in order to perform miRNA microarray analysis and to isolate and culture colonic epithelial cells. When differential expression of miRNA was found, the results were verified by qRT-PCR, and the target genes were further explored by bioinformatics analysis. Correlation analyses were carried out to compare the expression of miRNA and target genes. Then, mutants, miRNA mimics and inhibitors of the target genes were constructed and transfected to colonic epithelial cells. qRT-PCR, western blotting, enzyme-linked immunosorbent assays (ELISAs) and dual-luciferase assays were used to investigate the expression of miR-144 and OCLN, ZO1 in IBS-D rats. Results: There were 8 up-regulated and 18 down-regulated miRNAs identified in the IBS-D rat model. Of these, miR-144 was markedly up-regulated and resulted in the down-regulation of OCLN and ZO1 expression. Overexpression of miR-144 by transfection of miR-144 precursor markedly inhibited the expression of OCLN and ZO1. Further studies confirmed that OCLN and ZO1 were direct targets of miR-144. Additionally, intestinal hyperpermeability was enhanced by miR-144 up-regulation and attenuated by miR-144 down-regulation in IBS-D rat colonic epithelial cells. Moreover, rescue experiments showed that overexpression of OCLN and ZO1 significantly eliminated the inhibitory effect of miR-144, which showed a stronger effect on the attenuation of intestinal hyperpermeability. Conclusion: Up-regulation of miR-144 could promote intestinal hyperpermeability and impair the protective effect of the epithelial barrier by directly targeting OCLN and ZO1. miR-144 is likely a key regulator of intestinal hyperpermeability and could be a potential therapeutic target for IBS-D.

BackgroundThis review aims to critically appraise and compare the measurement properties of inflammatory bowel disease (IBD)-specific health-related quality of life instruments.MethodsMedline, EMBASE and ISI Web of Knowledge were searched from their inception to May 2016. IBD-specific instruments for patients with Crohn’s disease, ulcerative colitis or IBD were enrolled. The basic characteristics and domains of the instruments were collected. The methodological quality of measurement properties and measurement properties of the instruments were assessed.ResultsFifteen IBD-specific instruments were included, which included twelve instruments for adult IBD patients and three for paediatric IBD patients. All of the instruments were developed in North American and European countries. The following common domains were identified: IBD-related symptoms, physical, emotional and social domain. The methodological quality was satisfactory for content validity; fair in internal consistency, reliability, structural validity, hypotheses testing and criterion validity; and poor in measurement error, cross-cultural validity and responsiveness. For adult IBD patients, the IBDQ-32 and its short version (SIBDQ) had good measurement properties and were the most widely used worldwide. For paediatric IBD patients, the IMPACT-III had good measurement properties and had more translated versions.ConclusionsMost methodological quality should be promoted, especially measurement error, cross-cultural validity and responsiveness. The IBDQ-32 was the most widely used instrument with good reliability and validity, followed by the SIBDQ and IMPACT-III. Further validation studies are necessary to support the use of other instruments.Electronic supplementary materialThe online version of this article (10.1186/s12955-017-0753-2) contains supplementary material, which is available to authorized users.

We performed this review to clarify which dietary and lifestyle factors are related to gastroesophageal reflux disease. Through a systematic search of the PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Chinese BioMedical Literature (CBM) databases, we identified articles with clear definitions of GERD, including nonerosive gastroesophageal reflux disease (NERD), reflux esophagitis (RE) and Barrett’s esophagus (BE), that included dietary and lifestyle factors as independent factors affecting the onset of GERD (expressed as odds ratios (ORs) or relative risks (RRs) and 95% confidence intervals (CIs)). Due to heterogeneity among the studies, we used descriptive statistical analyses to analyze and synthesize each outcome based on the disease type. In total, 72 articles were included, conducted in ten Western countries (26 articles in total) and nine Eastern countries (46 articles in total). We categorized dietary factors into 20 items and lifestyle factors into 11 items. GERD is related to many irregular dietary and lifestyle habits (such as a habit of midnight snacking: OR=5.08, 95% CI 4.03–6.4; skipping breakfast: OR=2.7, 95% CI 2.17–3.35; eating quickly: OR=4.06, 95% CI 3.11–5.29; eating very hot foods: OR=1.81, 95% CI 1.37–2.4; and eating beyond fullness: OR=2.85, 95% CI 2.18–3.73). Vegetarian diets (consumption of nonvegetarian food (no/yes); OR=0.34, 95% CI 0.211–0.545) and no intake of meat (OR=0.841, 95% CI 0.715–0.990) were negatively related to GERD, while meat (daily meat, fish, and egg intake: OR=1.088, 95% CI 1.042-1.135) and fat (high–fat diet: OR=7.568, 95% CI 4.557–8.908) consumption were positively related to GERD. An interval of less than three hours between dinner and bedtime (OR=7.45, 95% CI 3.38–16.4) was positively related to GERD, and proper physical exercise (physical exercise >30 minutes (>3 times/week): OR=0.7, 95% CI 0.6–0.9) was negatively correlated with GERD. Smoking (OR=1.19, 95% CI 1.12–1.264), alcohol consumption (OR=1.278, 95% CI 1.207–1.353) and mental state (poor mental state: OR=1.278, 95% CI 1.207–1.353) were positively correlated with GERD. RE (vitamin C: OR=0.46, 95% CI=0.24–0.90) and BE (vitamin C: OR=0.44,95% CI 0.2-0.98; vitamin E: OR=0.46, 95% CI 0.26–0.83) were generally negatively correlated with antioxidant intake. In conclusion, many dietary and lifestyle factors affect the onset of GERD, and these factors differ among regions and disease types. These findings need to be further confirmed in subsequent studies.

Background/AimsMicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown.MethodsWe established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats.ResultsThe IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs.ConclusionsThis study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.