Abstract
For the past 10 years, research into peptic ulcer disease has focused on the surprising suggestion that gastritis and peptic ulcers may be caused by the bacterium Helicobacter pylori. However, the time has now come to reappraise research directions, as a causal link has been established, and even the most ardent sceptics now accept that H. pylori infection is the major factor in most cases of peptic ulcer disease. As with any established microbial disease, we need to understand the epidemiology and mechanisms of pathogenesis, but the major focus should be towards improving therapies and defining the long-term outcome of H. pylori eradication. To devise novel therapeutic agents effectively, we must increase our knowledge of the basic physiology of H. pylori and its ecology in the stomach. This has been a surprisingly neglected area of research and major questions remain. Why does the organism flourish in different areas of the gastric mucosa when gastric pH is increased? Is a change in pH the reason for the potentiating effects of acid-inhibitory agents on anti-H. pylori activity? Will knowledge of the host and bacterial factors that initiate ulcerogenesis allow us to better predict H. pylori-associated ulcers by using non-invasive methods? As H. pylori is a major gastroduodenal pathogen, can we eliminate the infection from selected populations? What are the criteria that will allow therapeutic intervention? The first steps have been taken in the development of an effective vaccine, but who should be immunized? As we move into the second decade of research on H. pylori, the question is not whether to treat, but how to treat more effectively. The focus of future research should be to understand better the physiology of H. pylori and its pathogenic interaction with the host, thus enabling the identification of new targets for therapeutic agents, to enhance eradication in vivo using existing or novel agents, to identify protective antigenic determinants of known structure, and to learn how to stimulate the common mucosal immune system.