Effects of proton pump inhibitor use on the esophageal microbial community.

BACKGROUND: Changes in the esophageal microbiome correlate with esophageal disease, but the effects of proton pump inhibitor (PPI) drugs are incompletely characterized. Our objective was to identify the effects of PPI use on the microbial community of the esophagus. METHODS: Mucosal biopsies of the distal esophagus were analyzed using a customized esophageal microbiome qPCR panel array (EMB). Patient demographics, use of PPIs, duration of use and dose were recorded. RESULTS: Fifty-eight patients were included. Mean age was 60.5 years. Ninety percent (52/58) of patients were on PPIs. Mean dose was 42.7 mg. Mean duration of use was 2.5 years. The use of PPIs led to a significant difference in absolute levels of only one organism, Actinomyces, in the entire array (p < 0.01). Among patients who used proton pump inhibitors, there was no significant association between dose and absolute levels of any organism. Similarly, there was no association between duration of use and absolute levels of any organism. CONCLUSIONS: PPI use does not seem to cause significant changes in the distal esophageal microbial community. Future studies with larger sample sizes and esophageal pH testing should be performed to determine the level of acidity and its relationship to the microbial community.

Oxyntic Gland Adenoma in a Patient With Refractory Reflux.

A 58-year-old African American male was referred for endoscopic evaluation due to a persistent nine-year history of reflux. Previous endoscopy nine years ago revealed a small hiatal hernia and chronic gastritis caused by Helicobacter pylori (H. pylori), which was treated with triple therapy. During the current endoscopic evaluation, findings consistent with reflux esophagitis were identified, along with the discovery of an incidental 6 mm sessile polyp in the gastric fundus. Pathological examination revealed the presence of an oxyntic gland adenoma (OGA). Otherwise, the stomach was found to be unremarkable endoscopically and histologically. OGA is a rare gastric neoplasm that is primarily observed in Japan, with very few reported cases in North America. Studies have suggested a potential association with antacids, while the role of H. pylori in the development of OGA remains controversial. Our patient's OGA was completely resected during the endoscopy, with no recurrence noted on the three-month follow-up.

Cervical Esophageal Adenocarcinoma Arising From Gastric Inlet Patch: A Benign Lesion With Malignant Potential.

Proximal esophageal adenocarcinoma is extremely rare. A gastric inlet patch is a lesion of ectopic gastric mucosa usually found in the cervical esophagus and is considered an incidental finding, but there is a risk for malignant transformation. We report the case of a 50-year-old male with gastroesophageal reflux disease with a 6-month history of progressive dysphagia and 20-pound weight loss. Upper endoscopy showed a malignant stricture with adjacent gastric inlet patch. Biopsies obtained from endoscopic ultrasonography showed adenocarcinoma. This case re-emphasizes careful examination of ectopic gastric mucosa and to consider biopsy if there is suspicion for malignant transformation.

Novel Ex Vivo Model to Examine the Mechanism and Relationship of Esophageal Microbiota and Disease.

Rates of esophageal cancer have increased over the last 40 years. Recent clinical research has identified correlations between the esophageal microbiome and disease. However, mechanisms of action have been difficult to elucidate performing human experimentation. We propose an ex vivo model, which mimics the esophagus and is ideal for mechanistic studies on the esophageal microbiome and resultant transcriptome. To determine the microbiome and transcriptome profile of the human distal esophagus, the microbiome was assessed in 74 patients and the transcriptome profile was assessed in 37 patients with and without Barrett's esophagus. Thereafter, an ex vivo model of the esophagus was created using an air-liquid interfaced (ALI) design. This design created a sterile apical surface and a nutrient-rich basal surface. An epithelial layer was grown on the apical surface. A normal microbiome and Barrett's microbiome was harvested and created from patients during endoscopic examination of the esophagus. There was a distinct microbiome in patients with Barrett's esophagus. The ex vivo model was successfully created with a squamous epithelial layer on the apical surface of the ex vivo system. Using this ex vivo model, multiple normal esophageal and Barrett's esophageal cell lines will be created and used for experimentation. Each microbiome will be inoculated onto the sterile apical surface of each cell line. The resultant microbiome and transcriptome profile on each surface will be measured and compared to results in the human esophagus to determine the mechanism of the microbiome interaction.

Microbiota Detection Patterns Correlate With Presence and Severity of Barrett's Esophagus.

Background: The microbiome has been increasingly associated with different disease processes, but its role in esophagus is largely unknown. Our goal was to determine the associations of the esophageal microbiota with Barrett's esophagus. Methods: A total of 74 patients were included in this prospective study, including 34 patients with Barrett's esophagus and 40 patients without Barrett's esophagus. Esophageal swabs were obtained from the uvula, and mucosal biopsies were obtained from the proximal esophagus and distal esophagus in each patient. The microbiome of each sample was assessed using a customized Esophageal Microbiome qPCR array (EMB). For each clinical sample, we completed a detection/non-detection analysis for each organism in the EMB. The limit of detection (LOD) for each target was established by analysis of plasmid dilutions. Results: Average age was 60.2 years. There were significantly different microbial detection patterns in patients with Barrett's esophagus compared to the control population. There were a greater number of organisms which had different likelihoods of detection in the distal esophagus, compared to the proximal esophagus or uvula. In addition, as the length of the Barrett's column increased, multiple organisms were less likely to be detected. This decreased likelihood occurred only in the distal esophagus. Beside Barrett's esophagus, no other demographic factors were associated with differences in detection patterns. Conclusions: Microbial community structures differ between patients with and without Barrett's esophagus. Certain organisms are less likely to be detected as the severity of Barrett's esophagus worsens. These results suggest that particular organisms may have a protective effect against the development of Barrett's esophagus.

Natural history, pathophysiology and evaluation of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common diseases encountered by both internists and gastroenterologists. GERD can cause a wide variety of symptoms ranging from heartburn and regurgitation to more atypical symptoms such as cough, chest pain, and hoarseness. The diagnosis is often times made on the basis of history and clinical symptomatology. The prevalence of GERD is currently estimated to be 8-33% with the incidence of disease only expected to increase over time. Although most cases of GERD can be diagnosed based on symptoms and clinical presentation, the diagnosis of GERD can be challenging when symptoms are atypical. In this review, we provide a comprehensive summary of the epidemiology, pathophysiology, evaluation and diagnosis of gastroesophageal reflux disease.

Microflora composition in the gastrointestinal tract in patients with Barrett's esophagus.

BACKGROUND: The incidence of esophageal adenocarcinoma (EAC) has been increasing over the last 40 years. While Barrett's esophagus is a known risk factor for the development of EAC, the role of the microflora in the development of EAC is still largely unknown and is being investigated further by multiple centers. Our goal was to identify trends in microflora composition along various aspects of the upper gastrointestinal tract in patients with Barrett's esophagus. METHODS: After obtaining institutional review board approval, 12 patients agreed to participate in the study. While endoscopy was performed for surveillance Barrett's monitoring, additional biopsies of esophageal mucosa were taken from the (I) proximal esophagus, (II) mid-esophagus, (III) distal esophagus, and (IV) Barrett's esophagus. Additional swabs were also taken from the uvula and the endoscope used during the procedure. The swabs from the uvula and endoscope were obtained prior to the endoscope entering the stomach, to prevent exposing the endoscope to the acidic environment of the stomach. The most common bacterial elements were identified by amplifying sample DNA using a panel of 5 "universal" fusion primer pairs. The 400-500 base pair fragments created an overlap which covered 95% of the bacterial 16s gene. RESULTS: Throughout the esophagus, 34 bacterial genera were found which had a relative abundance of >1.0. Streptococcal genera were prevalent in all aspects of the esophagus, ranging from 16% to 70% of the bacterial community. Haemophilus genera were uniquely abundant in the Barrett's esophageal tissue but relatively absent elsewhere in the upper gastrointestinal tract. Overall, the percentage of Gram-positive organisms was much higher in the proximal than distal esophagus. The microflora pattern obtained from the uvula and endoscopic swabs did not correlate with any of the tissue biopsies along any aspect of the esophagus. CONCLUSIONS: In patients with Barrett's esophagus, Streptococcal genera are widespread throughout the esophagus. Gram-positive genera tend to decrease as a percentage of overall flora distally. Obtaining a simple swab of the oropharynx or endoscope itself appears to be a poor substitute for tissue biopsy of esophageal mucosa when evaluating microflora patterns.

Microbiota of the Oropharynx and Endoscope Compared to the Esophagus.

The role of the microflora in the development of esophageal disease is still largely unknown and is being investigated in more detail. Our goal was to determine how the microbiota levels of endoscope and uvular swabs compared to the levels of tissue biopsies along various points of the esophagus. 17 patients with Barrett's esophagus agreed to participate in the study. Biopsies of esophageal mucosa were taken from the (1) proximal esophagus, (2) mid-esophagus, (3) distal esophagus, and (4) Barrett's esophagus. Swabs were also taken from the uvula and the endoscope. Throughout the esophagus, 17 bacterial genera were detected from the samples. The microflora pattern obtained from the uvula and endoscopic swabs did not correlate well with mucosal biopsies along any aspect of the esophagus. There were statistically significant differences in the levels and proportions of bacteria found when comparing the uvula swab to the esophageal biopsies and when comparing the endoscope swab to the esophageal biopsies. Obtaining a simple swab of the uvula or endoscope itself appears to be a poor substitute for tissue biopsy of esophageal mucosa when evaluating microflora patterns. When performing microflora studies of the esophagus, mucosal biopsies should be used for analysis.

Recent and currently emerging medical treatment options for the treatment of alcoholic hepatitis.

Patients with severe alcoholic hepatitis (AH) need to be treated with specific treatment for better outcome. Currently available specific treatment modalities are use of corticosteroids or pentoxifylline. However, the response rate to these drugs is only about 50%-60%. Hence, there is an urgent need for better and more effective treatment options. Tumor necrosis factor plays an important role in the pathogenesis of AH. However, agents blocking the action of tumor necrosis factor have not been found to be effective. Rather the randomized studies evaluating these agents showed an adverse effect and more infections in treated patients. Critical role of tumor necrosis factor in hepatic regeneration explaining this contrast is discussed. Oxidative stress and inflammation derived from gut bacteria ate two main components in the pathogenesis of AH laying foundation for the role of antioxidants, probiotics, and antibiotics in the management of AH. This article reviews the current data and status of these newer agents for the treatment of AH. Of the various options available, Vitamin E and N-acetylcysteine (NAC) have shown great promise for clinical use as adjunct to corticosteroids. With these encouraging data, future well designed studies are suggested to assess Vitamin E and NAC before their routine use in clinical practice in the management of AH.