Microbial Exposures and Other Early Childhood Influences on the Subsequent Function of the Immune System

Abstract

A striking increase in chronic inflammatory disorders such as allergies, autoimmunity and inflammatory bowel diseases started in Europe in the mid-nineteenth century. There is powerful evidence that these increases are at least partly attributable to faulty regulation of the immune system resulting from lack of exposure to microorganisms that were tasked by coevolutionary processes with establishing the “normal” balances of effector mechanisms and the normal levels of regulation within the immune system. A Darwinian analysis of the evidence suggests that this is an example of “evolved dependence” on organisms (“Old Friends”) that coevolved with mammals and already accompanied early hominids in the Palaeolithic. Interestingly the relevant organisms are associated with human faeces, animals and mud. These organisms may form part of the microbiota or establish stable carrier states, while others are encountered continuously in primitive environments as “pseudocommensals” from mud and water. These organisms were not lost during the 1st epidemiological (Neolithic) transition, which might even have resulted in increased exposure to them, since their sources (faeces, animals and mud) remained abundant. However, the crucial organisms are lost progressively as populations undergo the second epidemiological transition (modern urban environment), and there is simultaneously a change in the nature and diversity of the important (and immunoregulatory) gut microbiota. By contrast, recently evolved sporadic “childhood infections” are not likely to have evolved immunoregulatory roles, and epidemiology supports this contention. The consequences of loss of “Old Friends” and distortion of the microbiota are aggravated by other modern environmental changes that also disturb regulation of the immune system (diet, obesity, vitamin D deficiency, pollution (dioxins), etc.). The more we understand how the microbiology of modern city-dwelling humans differs from that of our hunter-gatherer ancestors, the more we will be able to devise new ways to prevent and treat the chronic inflammatory disorders and stop their incidences from increasing in developing countries as they have in the rich ones. This must constitute one of the most potentially exciting branches of Darwinian medicine.