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Most studies on the relationship between childhood adversity and negative outcomes across the lifespan have focused on individual exposures or outcomes—an approach that has been limited in its ability to elucidate mechanisms or causality. We propose a new framework for examining the relationship between childhood adversity and negative outcomes—the bio-exposome. In this model, we aim to understand the interconnections between every aspect of biology and the exposome, and the way disparate biological and exposome factors shape, and are shaped by, one another. Once we understand when, in which contexts and towards whom stress calibration interventions should be targeted, through examination of the bio-exposome, we could facilitate prevention of some of the major causes of morbidity across the lifespan. To examine the bio-exposome, we offer a new research agenda that embraces …