Review article: bacteria and pathogenesis of disease in the upper gastrointestinal tract - beyond the era of <i>Helicobacter pylori</i>

Background: Study of the upper gastrointestinal microbiome has shown that other bacteria besides <i>Helicobacter pylori</i> flourish despite the hostile environment. Whilst <i>H. pylori</i> is the most studied bacteria in this region with a defined role in inflammation and neoplasia, it is apparent that other bacteria may contribute to UGI disease. Aim: To review current knowledge of bacteria inhabiting the oesophagus, stomach and duodenum. Methods: Published studies on the upper gastrointestinal microbiome (extracted from PubMed during the last 20 years). Results: The stomach is a hostile environment for bacteria; however, recent studies categorising the microbiota have shown surprising results. <i>Helicobacter pylori</i> has been intensively studied since 1984 and recent sequencing analysis of other gastric microbiota shows that <i>H. pylori</i> is not alone. Composition can be influenced by acid suppression, gastritis and abundance of <i>H. pylori</i>. Eradication of <i>H. pylori</i>, whilst decreasing gastric cancer is associated with an increase in asthma, reflux and obesity. A future approach may be to selectively eradicate bacteria which predispose to inflammation and cancer as opposed to a comprehensive knockout policy. In the oesophagus, viridans streptococci are the most common bacteria influenced by both oral and gastric bacteria. Oesophagitis and Barrett's oesophagus are characterised by a significant decrease in Gram-positive bacteria and an increase in Gram-negative bacteria. An inverse association of <i>H. pylori</i> and oesophageal adenocarcinoma is described. The duodenal microbiome has been shown to influence small intestinal bacterial overgrowth, irritable bowel syndrome and coeliac disease. The numbers of bacteria recoverable by culture are variable in the stomach mucosa and gastric juice, typically 10²-10⁴ colony-forming units (CFU)/g or mL and in the oesophagus, up to 10⁴ bacteria per mm² mucosal surface. In the small bowel, in health, 10³ CFU/mL are normal. Conclusion: This review highlights current knowledge of upper gastrointestinal bacteria and associations with disease