Lihua Peng

Review article: fungal microbiota and digestive diseases

The role of the fungal microbiota in digestive diseases is poorly defined, but is becoming better understood due to advances in metagenomics.

Intestinal microbiota pathogenesis and fecal microbiota transplantation for inflammatory bowel disease

The intestinal microbiota plays an important role in inflammatory bowel disease (IBD). The pathogenesis of IBD involves inappropriate ongoing activation of the mucosal immune system driven by abnormal intestinal microbiota in genetically predisposed individuals. However, there are still no definitive microbial pathogens linked to the onset of IBD. The composition and function of the intestinal microbiota and their metabolites are indeed disturbed in IBD patients. The special alterations of gut microbiota associated with IBD remain to be evaluated. The microbial interactions and host-microbe immune interactions are still not clarified. Limitations of present probiotic products in IBD are mainly due to modest clinical efficacy, few available strains and no standardized administration. Fecal microbiota transplantation (FMT) may restore intestinal microbial homeostasis, and preliminary data have shown the clinical efficacy of FMT on refractory IBD or IBD combined with Clostridium difficile infection. Additionally, synthetic microbiota transplantation with the defined composition of fecal microbiota is also a promising therapeutic approach for IBD. However, FMT-related barriers, including the mechanism of restoring gut microbiota, standardized donor screening, fecal material preparation and administration, and long-term safety should be resolved. The role of intestinal microbiota and FMT in IBD should be further investigated by metagenomic and metatranscriptomic analyses combined with germ-free/human flora-associated animals and chemostat gut models.

MicroRNA-155 Is Involved in the Pathogenesis of Ulcerative Colitis by Targeting FOXO3a

Background:MicroRNAs (miRNAs) are important posttranscriptional regulators of gene expression. The precise role of miRNAs in ulcerative colitis (UC) is not completely understood. The purpose of this study was to identify miRNAs that are induced in patients with active UC and to assess the effect of miR-155 on improving intestinal inflammation. Methods:The miRNA profiles in patients with active UC (n = 20) and healthy subjects (n = 16) were examined using miRNA microarrays. miR-155 upregulation was confirmed by quantitative RT-PCR. Regulation of the target gene FOXO3a expression by miR-155 was assessed using luciferase reporter construct assays and miR-155 mimic or inhibitor transfections. The effects of FOXO3a or miR-155 on I&kgr;B&agr; or IL-8 were detected by Western blot or enzyme-linked immunosorbent assay in HT29 cells, respectively. Results:We identified 68 miRNAs that were differentially expressed (33 upregulated and 35 downregulated) in patients with active UC compared with healthy controls. One of the upregulated miRNAs in the UC tissue was miR-155 (1.22-fold, P < 0.03), which plays a key role in the regulation of inflammatory pathways. In patients with active UC, miR-155 was significantly upregulated, and the expression of FOXO3a dramatically decreased. Luciferase reporter assays demonstrated that miR-155 directly targets FOXO3a and affects the protein expression of FOXO3a in HT29 cells. Moreover, silenced FOXO3a and the overexpression of miR-155 increased the levels of IL-8 in TNF-&agr;–treated HT29 cells by suppressing the inhibitory I&kgr;B&agr;. Conclusions:miR-155 appears to play a role in the intestinal inflammation of patients with active UC by downregulating the expression of FOXO3a. This process may activate the nuclear factor kappa B signaling pathway.

Heterotopic gastric mucosa of the gastrointestinal tract: prevalence, histological features, and clinical characteristics.

Abstract Background. Heterotopic gastric mucosa (HGM) may be located at sites throughout the gastrointestinal (GI) tract. Clinical characteristics of HGM, role of Helicobacter pylori infection, natural history, and relationship to neoplastic transformation have not sufficiently been explored. Aim. To retrospectively study the prevalence, histological features, and clinical characteristics of HGM among Chinese patients who underwent upper GI endoscopy. Methods. Endoscopic, histological, and clinical records of patients, who underwent upper GI endoscopy (n = 6802) and colonoscopy (n = 3504), respectively, between May 2011 and May 2012, were collected and retrospectively analyzed. A total of 6716 sex- and age-matched patients without HGM were enrolled as controls. Results. HGM was diagnosed in 86 cases (51 esophageal, 0.75%; 35 duodenal, 0.51%). Male:female ratio was 1.4:1 (30/21) for esophageal HGM, 1.7:1 (22/13) for duodenal HGM, and 1.1:1 (3557/3159) for controls. Two histopathological types of HGM were identified: foveolar epithelium alone and foveoloar epithelium together with gastric glands. Helicobacter pylori were present in 19.6% of cases with esophageal HGM and 20.0% of cases with duodenal HGM. Esophageal HGM was significantly associated with dysphagia and globus; duodenal HGM was not significantly associated with GI symptoms. Intestinal metaplasia was present in two and three patients in both groups, respectively, with no dysplasia or carcinoma. Conclusion. HGM was present in fewer patients undergoing upper GI endoscopy, and it was more often present in men. A careful endoscopic examination is required to diagnose HGM, and it should be supported with a biopsy when indicated.

Influence of endoscopic submucosal dissection on esophageal motility.

AIM To assess esophageal motility after esophageal endoscopic submucosal dissection (ESD). METHODS Twelve patients (6 men and 6 women) aged 53-64 years (mean age, 58 years) who underwent regular examination 3-12 mo after esophageal ESD for neoplasms of the esophageal body were included in this study. The ESD procedure was performed under deep sedation using a combination of propofol and fentanyl, and involved a submucosal injection to lift the lesion and use of a dual-knife and an insulated-tip knife to create a circumferential incision around the lesion extending into the submucosa. Esophageal motility was examined using a high-resolution manometry system. Dysphagia was graded using a five-point scale according to the Mellow and Pinkas scoring system. Patient symptoms and the results of esophageal manometry were then analyzed. RESULTS Of the 12 patients enrolled, 1 patient had grade 2 dysphagia, 1 patient had grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Ineffective esophageal motility was observed in 5 of 6 patients with above semi-circumference of resection extension. Of these 5 patients, 1 patient complained of grade 2 dysphagia (with esophageal stricture), one patient complained of grade 1 dysphagia, and 3 patients complained of sporadic dysphagia. Normal esophageal body manometry was observed in all 6 patients with below semi-circumference of resection extension. The 6 patients with normal esophageal motility did not complain of dysphagia. CONCLUSION Extensive esophageal ESD may cause esophageal dysmotility in some patients, and might also have an influence on dysphagia although without esophageal stricture.

Initial meconium microbiome in Chinese neonates delivered naturally or by cesarean section

Previous studies have revealed significant differences in microbiome compositions between infants delivered via cesarean section (C-section) and natural vaginal birth. However, the importance of the delivery mode in the first days of life remains unclear. Importantly, this stage is minimally affected by infant feeding. Here, we used a metagenomic sequencing technique to characterize the meconium microbiome from the feces of a Chinese cohort of vaginally and C-section-delivered infants, including in vitro fertilization (IVF) newborns, during the first 24 h after birth. Meconium microbiome diversity was higher in vaginally delivered infants than that in C-section-delivered infants. Propionibacterium species were most abundant in the vaginally delivered infants, whereas the C-section group had high levels of Bacillus licheniformis. The two IVF newborns delivered by C-section harbored microbial communities similar to the vaginal microbiome in terms of taxonomic composition. Metabolic functions of the C-section group suffered more from the influence of the dominant group (B. licheniformis), whereas the vaginal group was more homogeneous, with a metabolism dominated by multi-microbes. Moreover, different modes of delivery affected the antibiotic resistance gene (ARG) prevalence. These findings provide novel information for the development of strategies to guide a healthy mode of delivery and promote the formation of healthy microbiota.

Autofluorescence imaging endoscopy can distinguish non-erosive reflux disease from functional heartburn: A pilot study

AIM To investigate whether autofluorescence imaging (AFI) endoscopy can distinguish non-erosive reflux disease (NERD) from functional heartburn (FH). METHODS In this prospective observational trial, 127 patients presenting with typical reflux symptoms for > 6 mo were screened. All the participants underwent endoscopy, during which white light imaging (WLI) was followed by AFI. Finally 84 patients with normal esophageal appearance on WLI were enrolled. It was defined as being suggestive of NERD if one or more longitudinal purple lines longer than one centimeter were visualized in the distal part of the esophagus during AFI endoscopy. Ambulatory 24-h multichannel intraluminal impedance and pH monitoring was also performed. After standard proton-pump inhibitor (PPI) tests, subjects were divided into an NERD group and an FH group and the diagnostic performance of AFI endoscopy to differentiate NERD from FH was evaluated. RESULTS Of 84 endoscopy-negative patients, 36 (42.9%) had a normal pH/impedance test. Of these, 26 patients with favorable responses to PPI tests were classified as having NERD. Finally 10 patients were diagnosed with FH and the others with NERD. Altogether, 68 (81.0%) of the 84 patients were positive on AFI endoscopy. In the NERD group, there were 67 (90.5%) patients with abnormal esophageal findings on AFI endoscopy while only 1 (10%) patient was positive on AFI endoscopy in the FH group. The sensitivity and specificity of AFI in differentiating NERD from FH were 90.5% (95%CI: 81.5%-96.1%) and 90.0% (95%CI: 55.5%-99.7%), respectively. Meanwhile, the accuracy, positive predictive value and negative predictive value of AFI in differentiating between NERD and FH were 90.5% (95%CI: 84.2%-96.8%), 98.5% (95%CI: 92.1%-99.9%) and 56.3% (95%CI: 30.0%-80.2%), respectively. CONCLUSION Autofluorescence imaging may serve as a complementary method in evaluating patients with NERD and FH.

Autofluorescence imaging endoscopy for predicting acid reflux in patients with gastroesophageal reflux disease

Endoscopic diagnosis of gastroesophageal reflux disease (GERD) remains challenging. Autofluorescence imaging (AFI) can identify indistinct mucosal lesions; however, its ability to diagnose GERD has not been determined. This study aimed to compare the diagnostic capabilities of standard white light imaging (WLI) and AFI using pH/impedance testing as gold standard.

The gastric mucosal-associated microbiome in patients with gastric polyposis

The characteristics of the gastric microbiota in patients with gastric polyposis (GP) remain unclear. Given this we collected gastric antrum and gastric body biopsies from healthy controls (HC.A and HC.B group) and gastric antrum, gastric body and polyp biopsies from patients with multiple gastric polyps (GP.A, GP.B and GP.P group) for 16S rDNA sequencing. The results showed that the diversity of the gastric flora in the GP group was significantly lower than that of the HC group. The gastric flora composition of the GP group was significantly different from the HC group. However, flora diversity and compositions in different parts of the stomach (gastric antrum, gastric body or polyp tissue) were not significantly different. H. pylori abundance could influence the composition of gastric microbiota. Meanwhile, patients with fundic gland polyps (FGPs) and those with hyperplastic polyps (HPs) had considerably similar gastric bacterial compositions. We constructed a microbial dysbiosis index (MDI) based on the gastric microbiota at the genus level as a predictive model, and it was able to distinguish between individuals in the GP and HC groups. These findings showed that intragastric flora dysbiosis may be closely related to the occurrence and development of gastric polyps.

Characteristics of fecal microbiota in non-alcoholic fatty liver disease patients

This study was designed to investigate the gut microbiota of patients with non-alcoholic fatty liver disease. The inclusive and exclusive criteria for NAFLD patients and healthy subjects were formulated, and detailed clinical data were collected. The genomic DNA of stool samples were extracted for 16S rDNA sequencing, and the amplified V4-region was sequenced on the Illumina Miseq platform. Metastats analysis was performed to identify the differential taxa between the groups. Redundancy analysis was used to evaluate the association between gut microbial structure and clinical variables. Thirty NAFLD patients and 37 healthy controls were involved. The 16S rDNA sequencing showed that there was a dramatic variability of the fecal microbiota among all the individuals. Metastats analysis identified eight families and 12 genera with significant differences between the two groups. When some clinical parameters, such as waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR), were enrolled in Redundancy analysis, the distribution of the two group of samples was obviously changed. The compositional shifts in fecal bacterial communities of NAFLD patients from the healthy controls were mainly at family or genus levels. According to our Redundancy analysis, insulin resistance and obesity might be closely related to both NAFLD phenotype and intestinal microecology.