Enteric microbiota leads to new therapeutic strategies for ulcerative colitis.

Ulcerative colitis (UC) is a leading form of inflammatory bowel disease that involves chronic relapsing or progressive inflammation. As a significant proportion of UC patients treated with conventional therapies do not achieve remission, there is a pressing need for the development of more effective therapies. The human gut contains a large, diverse, and dynamic population of microorganisms, collectively referred to as the enteric microbiota. There is a symbiotic relationship between the human host and the enteric microbiota, which provides nutrition, protection against pathogenic organisms, and promotes immune homeostasis. An imbalance of the normal enteric microbiota composition (termed dysbiosis) underlies the pathogenesis of UC. A reduction of enteric microbiota diversity has been observed in UC patients, mainly affecting the butyrate-producing bacteria, such as Faecalibacterium prausnitzii, which can repress pro-inflammatory cytokines. Many studies have shown that enteric microbiota plays an important role in anti-inflammatory and immunoregulatory activities, which can benefit UC patients. Therefore, manipulation of the dysbiosis is an attractive approach for UC therapy. Various therapies targeting a restoration of the enteric microbiota have shown efficacy in treating patients with active and chronic forms of UC. Such therapies include fecal microbiota transplantation, probiotics, prebiotics, antibiotics, helminth therapy, and dietary polyphenols, all of which can alter the abundance and composition of the enteric microbiota. Although there have been many large, randomized controlled clinical trials assessing these treatments, the effectiveness and safety of these bacteria-driven therapies need further evaluation. This review focuses on the important role that the enteric microbiota plays in maintaining intestinal homeostasis and discusses new therapeutic strategies targeting the enteric microbiota for UC.

Implication of miRNAs for inflammatory bowel disease treatment: Systematic review.

Inflammatory bowel disease (IBD) is believed to develop via a complex interaction between genetic, environmental factors and the mucosal immune system. Crohn's disease and ulcerative colitis are two major clinical forms of IBD. MicroRNAs (miRNAs) are a class of small, endogenous, noncoding RNA molecules, and evolutionary conserved in animals and plants. It controls protein production at the post-transcriptional level by targeting mRNAs for translational repression or degradation. MiRNAs are important in many biological processes, such as signal transduction, cellular proliferation, differentiation and apoptosis. Considerable attention has been paid on the key role of miRNAs in autoimmune and inflammatory disease, especially IBD. Recent studies have identified altered miRNA profiles in ulcerative colitis, Crohn's disease and inflammatory bowel disease-associated colorectal cancer. In addition, emerging data have implicated that special miRNAs which suppress functional targets play a critical role in regulating key pathogenic mechanism in IBD. MiRNAs were found involving in regulation of nuclear transcription factor kappa B pathway (e.g., miR-146a, miR-146b, miR-122, miR-132, miR-126), intestinal epithelial barrier function (e.g., miR-21, miR-150, miR-200b) and the autophagic activity (e.g., miR-30c, miR-130a, miR-106b, miR-93, miR-196). This review aims at discussing recent advances in our understanding of miRNAs in IBD pathogenesis, their role as disease biomarkers, and perspective for future investigation and clinical application.

Addition of prokinetics to PPI therapy in gastroesophageal reflux disease: a meta-analysis.

AIM: To investigate the efficacy of adding prokinetics to proton pump inhibitors (PPIs) for the treatment of gastroesophageal reflux disease (GERD). METHODS: PubMed, Cochrane Library, and Web of Knowledge databases (prior to October 2013) were systematically searched for randomized controlled trials (RCTs) that compared therapeutic efficacy of PPI alone (single therapy) or PPI plus prokinetics (combined therapy) for GERD. The primary outcome of those selected trials was complete or partial relief of non-erosive reflux disease symptoms or mucosal healing in erosive reflux esophagitis. Using the test of heterogeneity, we established a fixed or random effects model where the risk ratio was the primary readout for measuring efficacy. RESULTS: Twelve RCTs including 2403 patients in total were enrolled in this study. Combined therapy was not associated with significant relief of symptoms or alterations in endoscopic response relative to single therapy (95%CI: 1.0-1.2, P = 0.05; 95%CI: 0.66-2.61, P = 0.44). However, combined therapy was associated with a greater symptom score change (95%CI: 2.14-3.02, P < 0.00001). Although there was a reduction in the number of reflux episodes in GERD [95%CI: -5.96-(-1.78), P = 0.0003] with the combined therapy, there was no significant effect on acid exposure time (95%CI: -0.37-0.60, P = 0.65). The proportion of patients with adverse effects undergoing combined therapy was significantly higher than for PPI therapy alone (95%CI: 1.06-1.36, P = 0.005) when the difference between 5-HT receptor agonist and PPI combined therapy and single therapy (95%CI: 0.84-1.39, P = 0.53) was excluded. CONCLUSION: Combined therapy may partially improve patient quality of life, but has no significant effect on symptom or endoscopic response of GERD.