Hallmarks of environmental insults

Abstract

Environmental insults impair human health around the world. Contaminated air, water, soil, food, and occupational and household settings expose humans of all ages to a plethora of chemicals and environmental stressors. We propose eight hallmarks of environmental insults that jointly underpin the damaging impact of environmental exposures during the lifespan. Specifically, they include oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction, endocrine disruption, altered intercellular communication, altered microbiome communities, and impaired nervous system function. They provide a framework to understand why complex mixtures of environmental exposures induce severe health effects even at relatively modest concentrations.

Figure 1:. Hallmarks of environmental insults.

The scheme enumerates the hallmarks of environmental insults described in this review: Oxidative stress and inflammation, genomic alterations and mutations, epigenetic alterations, mitochondrial dysfunction, endocrine disruption, altered intercellular communication, altered microbiome communities, and impaired nervous system function.

Figure 2:. Role of reactive oxygen species as agents for exhibiting environmental insults.

Environmental exposures challenge the cells based on their reactive oxygen potential, their concentrations, and the duration of exposures. While the cells are able to tolerate certain exposures, others elicit adaptation or inflammatory responses. Overwhelming oxidative stress results in cell death and organ damage. The activation of the NRF2 and NF-κB pathways activated by particulate matter air pollution in lung epithelial cells (Mudway et al., 2020) are depicted as examples.

Figure 3:. Environmental insults and protective factors for the lung and the gut microbiome.

Complex urban and traditional farm environments alter the microbiome variability and the immune function at the barrier organs and have been implicated to either promote or protect against allergies.

Figure 4:. Illustration of organ-specific impacts based on the hallmarks of environmental insults.

These pathophysiological changes summarize examples of how environmental exposures impact organs locally as well as exhibit their insults systemically.