Categorizing biomarkers of the human exposome and developing metrics for assessing environmental sustainability

The concept of maintaining environmental sustainability broadly encompasses all human activities that impact the global environment, including the production of energy, use and management of finite resources such as petrochemicals, metals, food production (farmland, fresh and ocean waters), and potable water sources (rivers, lakes, aquifers), as well as preserving the diversity of the surrounding ecosystems. The ultimate concern is how one can manage Spaceship Earth in the long term to sustain the life, health, and welfare of the human species and the planet's flora and fauna. On a more intimate scale, one needs to consider the human interaction with the environment as expressed in the form of the exposome, which is defined as all exogenous and endogenous exposures from conception onward, including exposures from diet, lifestyle, and internal biology, as a quantity of critical interest to disease etiology. Current status and subsequent changes in the measurable components of the exposome, the human biomarkers, could thus conceivably be used to assess the sustainability of the environmental conditions with respect to human health. The basic theory is that a shift away from sustainability will be reflected in outlier measurements of human biomarkers. In this review, the philosophy of long-term environmental sustainability is explored in the context of human biomarker measurements and how empirical data can be collected and interpreted to assess if solutions to existing environmental problems might have unintended consequences. The first part discusses four conventions in the literature for categorizing environmental biomarkers and how different types of biomarker measurements might fit into the various grouping schemes. The second part lays out a sequence of data management strategies to establish statistics and patterns within the exposome that reflect human homeostasis and how changes or perturbations might be interpreted in light of external environmental stressors. The underlying concept is to identify probative outliers from the "unremarkable exposome" in individuals or subpopulations that could be used for discerning deviations from the healthy environment, much like current diagnostic medicine uses batteries of blood and urine tests to screen for preclinical disease conditions. Such empirically derived human in vivo data could subsequently be integrated into high-throughput in vitro and in silico testing of environmental and manufactured chemicals to support real-world toxicity evaluations.