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.

The manifestations of gastroesophageal reflux disease (GERD) have been classified into either esophageal or extraesophageal syndromes. Cough, reflux laryngitis, and asthma have been classified as extraesophageal syndromes, whereas reflux chest pain has been classified as a symptomatic syndrome of GERD. In extraesophageal syndromes, patients usually do not display the classic symptoms of reflux, such as heartburn and regurgitation. Upper gastrointestinal endoscopy and pH monitoring, when used to diagnose reflux in patients with symptoms not classic for GERD, have proved to have poor sensitivity and are often not diagnostically helpful. In contrast, an empiric trial of proton pump inhibitors is a well-established, cost-effective tool.

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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.

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. 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.