It is becoming increasingly clear that our residential microbes, the key constituents in the human microbiome, are centrally involved in many aspects of our physiology. In particular, the ancient and dominant gastric bacteria Helicobacter pylori are highly interactive with human physiology. In modern times, H. pylori has been disappearing, which consequently affects the interactions between luminal bacteria and epithelial, lymphoid, and neuroendocrine cells. A growing body of evidence indicates that H. pylori protects against childhood-onset asthma, probably through the gastric recruitment of regulatory T cells. The phenomenon of disappearing ancient microbiota may be a general paradigm driving the diseases of modernity.