Childhood food allergies: An evolutionary mismatch hypothesis

For hominins living in the Paleolithic era, early food antigen exposures-in utero and throughout infancy-closely matched later exposures, and therefore immune system tolerance mechanisms evolved under the expectation of this condition being met. This predicts that the degree of mismatch between early and downstream food antigen exposures is a key variable underlying the development of childhood food allergies. Three historical periods are identified in which the degree of mismatch climbs from near zero to substantial, as we transition from one period to another. The first encompasses our long history as foragers; the second begins with the advent of farming and the third spans only the most recent two or three decades, and manifests from social changes driven largely by an explosion in access to information. Testable predictions are generated and evaluated in light of available evidence, and an approach for primary prevention of childhood food allergies is proposed.