Darwinian Medicine: We Evolved to Require Continuing Contact with the Microbiota of the Natural Environment. Evolution Turns the Inevitable into a Necessity

The immune system requires data inputs, especially in early life. A lack of these inputs contributes to increases in immunoregulatory disorders such as those in which the immune system attacks inappropriate targets (harmless allergens, self-components, or gut contents) or fails to switch off unnecessary background inflammation (resulting in chronically raised biomarkers of inflammation, and cardiovascular, metabolic, and psychiatric disorders). We can use an evolutionary approach to identify inputs that the immune systems of evolving humans inevitably received, because these are the inputs on which we may be in a state of “evolved dependence”. The maternal microbiota is clearly one major source of data for the developing immune system, and we now understand that caesarean deliveries, lack of breastfeeding, unvaried diets, and misuse of antibiotics are distorting mother-to-child transmission of the microbiota. However, the main focus of this essay is the crucial role of inputs from the natural environment, which have received much less attention despite the fact that epidemiology reveals strong health benefits of contact with nature. These inputs from nature, received via the airways, gut, and skin, provide crucial signals that set up immunoregulatory circuits. The natural environment also provides other inputs including epitopes to guide retention and expansion of useful lymphocyte clones, information about the microbiota of the environment into which the individual is born, signals that drive background activation of the innate immune system, spores of gut-adapted strains that can replace those lost because of antibiotics or poor diet, bacteriophages that modulate the microbiota, and DNA via horizontal gene transfer that increases metabolic flexibility of the gut microbiota. By analysing these microbial inputs and their mechanisms of action, while also identifying the lifestyle changes that are disrupting them, we can expect to discover novel prophylactic and therapeutic strategies.