The Esophageal Microbiome in Health and Disease.

PURPOSE OF REVIEW: Investigation of the esophageal microbiome is a relatively new field. This review will outline data characterizing the esophageal microbiome in both health and disease states, including gastroesophageal reflux disease (GERD), Barrett's esophagus, esophageal cancer, eosinophilic esophagitis, and motility disorders. RECENT FINDINGS: While the esophagus was previously considered devoid of a significant bacterial population, development of culture-independent techniques, specifically 16S rRNA gene sequencing, as well as novel, minimally invasive microbial sampling modalities, has facilitated characterization of the esophageal microbiome in both health and several disease states. Although limited, there is evidence that the esophagus contains a diverse microbial population, with Gram-positive bacteria, specifically Streptococcus, dominating in health, while Gram-negative bacteria prevail in reflux disorders including GERD and Barrett's esophagus. The microbiome is altered with other esophageal disorders as well, including eosinophilic esophagitis and esophageal motility disorders, though these changes have been less well characterized. Characterization of the gut microbiome has advanced significantly; however, further investigation is essential. Understanding changes in the esophageal microbiome could affect our understanding of the natural history of diseases of the esophagus and present potential therapeutic approaches.

Interstitial Lung Disease in a 70-Year-Old Man with Ulcerative Colitis.

Interstitial lung disease is a rare but increasingly recognized extraintestinal manifestation of inflammatory bowel disease that can have devastating consequences if left untreated. We report a case of ulcerative colitis-associated interstitial lung disease presenting with acute hypoxic respiratory failure during an ulcerative colitis flare. Gastroenterologists and pulmonologists should be aware of the numerous bronchopulmonary signs and symptoms that can suggest systemic illness in inflammatory bowel disease.

Celiac Disease and Gluten Sensitivity.

Celiac disease is an immune-mediated enteropathy triggered by gluten that affects genetically predisposed individuals, typically causing intestinal symptoms and malabsorption. Diagnosis requires stepwise evaluation with anti-tissue transglutaminase IgA and histologic analysis of the small bowel. Strict adherence to a gluten-free diet is the primary treatment. Patients with symptoms thought to be related to gluten but without evidence of celiac disease are difficult to diagnose and treat. Consider first advising general nutritional improvements. If symptoms persist, involve a trained dietitian for restrictive diets and consider evaluation for small intestinal bacterial overgrowth or other treatments for irritable bowel syndrome.

Gastric intestinal metaplasia is associated with gastric dysplasia but is inversely correlated with esophageal dysplasia.

AIM: To determine which clinical factors might be associated with gastric intestinal metaplasia (IM) in a North American population. METHODS: Pathology and endoscopy databases at an academic medical center were reviewed to identify patients with and without gastric IM on biopsies for a retrospective cohort study. Patient demographics, insurance status, and other clinical factors were reviewed. RESULTS: Four hundred and sixty-eight patients with gastric IM (mean age: 61.0 years ± 14.4 years, 55.5% female) and 171 without gastric IM (mean age: 48.8 years ± 20.8 years, 55.0% female) were compared. The endoscopic appearance of atrophic gastritis correlated with finding gastric IM on histopathology (OR = 2.05, P = 0.051). Gastric IM was associated with histologic findings of chronic gastritis (OR = 2.56, P < 0.001), gastric ulcer (OR = 6.97, P = 0.015), gastric dysplasia (OR = 6.11, P = 0.038), and gastric cancer (OR = 6.53, P = 0.027). Histologic findings of Barrett's esophagus (OR = 0.28, P = 0.003) and esophageal dysplasia (OR = 0.11, P = 0.014) were inversely associated with gastric IM. Tobacco use (OR = 1.73, P = 0.005) was associated with gastric IM. CONCLUSION: Patients who smoke or have the endoscopic finding of atrophic gastritis are more likely to have gastric IM and should have screening gastric biopsies during esophagogastroduodenoscopy (EGD). Patients with gastric IM are at increased risk for having gastric dysplasia and cancer, and surveillance EGD with gastric biopsies in these patients might be reasonable.

Managing gastroesophageal reflux disease - comparative efficacy and outcomes of dexlansoprazole MR.

The management of gastroesophageal reflux disease (GERD) has been revolutionized with the development of proton pump inhibitors (PPIs). Unfortunately, due to the inherent pharmacokinetic and pharmacodynamic profiles of conventional PPIs, many patients continue to suffer from symptoms related to GERD despite appropriate use of PPIs. Dexlansoprazole MR is a PPI with a unique dual delayed-release delivery system that has been designed to address the unmet needs in GERD management. Specifically, dexlansoprazole MR addresses limitations with short plasma half-life and need for meal-associated dosing, characteristic of conventional PPIs. In addition, dexlansoprazole MR has been shown to be effective in several specific clinical situations. These include coadministration with clopidogrel, healing of all grades of erosive esophagitis, improvement in reflux-related quality of life, step down to once-per-day dosing, and treatment of Helicobacter pylori infections. Furthermore, dexlansoprazole MR has been found to induce symptom improvement in patients with nonerosive esophageal reflux disease, nocturnal heartburn and GERD-related sleep disturbance, and regurgitation. Overall, dexlansoprazole MR is a unique and useful tool in the management of GERD.

Spermine oxidase is a regulator of macrophage host response to Helicobacter pylori: enhancement of antimicrobial nitric oxide generation by depletion of spermine.

The gastric pathogen Helicobacter pylori causes peptic ulcer disease and gastric cancer. We have reported that in H. pylori-activated macrophages, nitric oxide (NO) derived from inducible NO synthase (iNOS) can kill the bacterium, iNOS protein expression is dependent on uptake of its substrate L-arginine (L-Arg), the polyamine spermine can inhibit iNOS translation by inhibiting L-Arg uptake, and inhibition of polyamine synthesis enhances NO-mediated bacterial killing. Because spermine oxidase (SMO), which back-converts spermine to spermidine, is induced in macrophages by H. pylori, we determined its role in iNOS-dependent host defense. SMO shRNA knockdown in RAW 264.7 murine macrophages resulted in a marked decrease in H. pylori-stimulated iNOS protein, but not mRNA expression, and a 90% reduction in NO levels; NO production was also inhibited in primary murine peritoneal macrophages with SMO knockdown. There was an increase in spermine levels after H. pylori stimulation that rapidly decreased, while SMO knockdown caused a greater increase in spermine that was sustained. With SMO knockdown, L-Arg uptake and killing of H. pylori by macrophages was prevented. The overexpression of SMO by transfection of an expression plasmid prevented the H. pylori-stimulated increase in spermine levels, and led to increased L-Arg uptake, iNOS protein expression and NO production, and H. pylori killing. In two human monocytic cell lines, U937 and THP-1, overexpression of SMO caused a significant enhancement of NO production with H. pylori stimulation. By depleting spermine, SMO can abrogate the inhibitory effect of polyamines on innate immune responses to H. pylori by enhancing antimicrobial NO production.

Perioperative risk assessment for patients with cirrhosis and liver disease.

Patients with cirrhosis are at an increased risk of complications of operative procedures. There is a growing understanding of the nature of the risks that cirrhotic patients experience, as well as more precise and objective tools to gauge the patients at risk for surgical complications. Surgical procedures that are common and high risk for patients with cirrhosis are cardiac surgery, cholecystectomy and hepatic resections, as well as other abdominal surgeries and orthopedic surgeries. The physicians who care for patients with cirrhosis who require a surgical procedure can apply an understanding of the type of surgery anticipated with knowledge of the severity of the patient's liver disease to predict those patients at risk for operative morbidity and mortality. A sound knowledge of the specific operative risks faced by patients with cirrhosis should prompt the clinician to take steps to prevent these complications.