Childhood microbial experience, immunoregulation, inflammation, and adult susceptibility to psychosocial stressors and depression

Microbial exposures early in life modulate our susceptibility to depression via effects on the composition of the microbiota and the development of the immune system. Modern urban lifestyles reduce these exposures resulting in altered microbiota and defective regulation of inflammatory responses. These changes are reflected in the increasing prevalence of chronic inflammatory disorders and of persistently raised biomarkers of inflammation among those living in modern urban societies, compared with those living a hunter-gatherer or subsistence agriculture-based lifestyle. Moreover, the microbiota regulates metabolism, so a distorted microbiota can promote obesity and the associated inflammation. Similarly, the microbiota regulates the size of the inflammatory response to psychosocial stressors. Thus, there are multiple links between childhood exposures to microbes and the later presence of persistent inflammation that contributes to the risk of depression. Here, we evaluate the evidence for the impact of childhood microbial exposures on subsequent vulnerability to stress-related psychiatric disorders.