26 Gut and Liver, Vol. 6, No. 1, January 2012 has been declining steadily, especially in younger individuals. This results in cohorts that have never been infected with H. pylori. In most subjects, H. pylori is commensal, not related to disease. It is hypothesized that the loss of the natural balance between the two species may result in disease and the total absence of H. pylori for life has been linked to new epidemics being observed at the present time. One such epidemic is the ad- enocarcinoma of the lower esophagus, linked to reflux esopha- gitis and Barrett’s esophagus. These may reflect relatively exces- sive gastric acid secretion, which could be linked to the absence of H. pylori infection. Other diseases apparently increasing in frequency lately are allergic disease such as asthma and autoim- mune diseases. It has been proposed that these new epidemics may be related to the so-called hygiene hypothesis.70 Exposure to H. pylori and other infections during childhood may drive a Th1 (pro-inflammatory) immune response that may set a pat- tern of response to later antigenic stimuli. In the absence of infections, antigenic stimuli after the childhood years may lead to Th2 (allergic) immune responses, linked to asthma. This hy- pothesis has been recently supported in an animal model.71 CONFLICTS OF INTEREST No potential conflict of interest relevant to this article was reported. ACKNOWLEDGEMENTS This work was supported by the grant P01-CA28842 from the U.S. National Cancer Institute. REFERENCES 1. Helicobacter and Cancer Collaborative Group. Gastric cancer and Helicobacter pylori: a combined analysis of 12 case control studies nested within prospective cohorts. Gut 2001;49:347-353. 2. Peek RM Jr, Crabtree JE. Helicobacter infection and gastric neo- plasia. J Pathol 2006;208:233-248. 3. 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