The coevolved relationship between <italic>Helicobacter pylori</italic> and human

Helicobacter pylori ( H. pylori ) is a known pathogen of human stomach which is linked to gastric adenocarcinoma, and antibiotic therapy is commonly used for H. pylori eradication. However, accumilating data have formed enough testimony to convey that H. pylori may have coevolved with human host as symbiotic flora rather than pathogenic bacteria. Firstly, a majority of infected individuals are asymptomatic; only a small fraction of infected individuals develop H. pylori -associated diseases, such as peptic ulcers and, more rarely, gastric adenocarcinomas. Secondly, H. pylori has colonization in human stomach for a long time. Genetic evidences have suggested that H. pylori is one of the oldest and most common occupants of the human gastric microbiome, arriving before the migration out of Eastern Africa over 60000 years ago. Thirdly, H. pylori can confer a benefit to human health. Since mutual benefits obliged both partners to adapt themselves in order to establish stable symbiosis, it is therefore possible that the bacterium confers a benefit to its host under some circumstances and is therefore maintained in the human population. It has been suggested that H. pylori can be beneficial for host health in several aspects, including regression in child asthma and other allergic disorders, confering protection against tuberculosis (TB) through induction of antagonistic interferons for the causative agent, Mycobacterium tuberculosis , and playing a role in reducing the risk of esophageal adenocarcinoma (EAC), gastroesophageal reflux disease, stroke, lung cancer, asthma, allergies, and inflammatory bowel disease. We need rethinking the complexity relationship between H. pylori and human, and the impact of this bacterium on human health. Elimination of H. pylori as permanent resident of human microbiome would not be the first option to deal with gastroduodenal diseases, and the long cohabitation in our stomach calls for more deep studies to elucidate microbiota and human health. In this review, we aim to elucidate the secret of H. pylori infection inducing gastric adenocarcinomas. The coevolved relationship between H. pylori and human may help us understanding why a majority of infected individuals are asymptomatic, while a small fraction of infected individuals develop gastric adenocarcinomas. Thus, we elucidate the detail about the long period of H. pylori gastric colonization for 60000 years, and the highly adaptable strategies used by H. pylori to make a lifelong colonization, which has been obtained in the longtime coevolved with human. On basis of these, we discuss the impact of H. pylori on human health, and explore future therapeutic strategies for disease management in light of the longstanding evolutionary history between H. pylori and its human host. We suggest that disrupted coevolution between a pathogen and its human host can induce diseases like gastric adenocarcinoma, and maintaining symbiosis is key for effective detection, management, and disease prevention.