(A) Ancient, premodern, and postmodern stomachs. From ancient times, normal human physiology in the presence of H. pylori pan-gastritis has avoided disease until the gastric cancers of old age. We speculate that premodern changes in the pattern of colonization and inflammation in the stomach resulted in changes in physiology and the rise of peptic ulcer disease (PUD). In the postmodern (current) era, the absence of H. pylori leads to distorted physiology, to which we have not fully adapted. This may have led to disease in some children and adults but avoids gastric cancer in old age. (B) A model of the proposed biphasic nature of H. pylori and human disease. Because we have coevolved with H. pylori, the changed physiology resulting from an H. pylori–free stomach may contribute to some modern diseases. Thus, from a postmodern viewpoint, H. pylori may confer benefits to humans early in their life span. Possible examples include reducing infectious diseases, controlling allergy, regulating gastric hormones such as leptin and ghrelin (benefits uncertain), and reducing gastroesophageal reflux disease sequelae. Later in life, H. pylori has biological costs, inducing ulcers, (possible) metabolic disturbances, anemia, and gastric cancers, all more prominent in an ageing population. In both A and B, black text indicates information for which there is strong evidence — for these, the balance is toward a net deleterious effect of H. pylori on human health — and red text indicates information for which evidence remains under debate. cag-negative strains are less interactive with humans, conferring smaller risks and putative benefits.