Lethal exposure can have fatal consequences. On the contrary, small-dose exposures to certain stimuli can exert beneficial effects on humans through hormesis interactions. These adaptive responses prime various defense mechanisms, such as hormonal adaptations, autonomic nervous system activations, cell signaling, redox homeodynamics, immune responses, unfolded protein responses, mitophagy, or autophagy. The preceding training builds up diverse biological shields that create tolerance for potential future threats.
The consumption of a polyphenol-rich diet is an example of hormesis-induced tolerance. With high-dose exposures, these plant secondary metabolites have strong prooxidant, antimicrobial, and mutagenic effects. However, these same polyphenols show beneficial effects when consumed as part of a diet. Their antioxidant and anti-inflammatory properties are believed to be mediated by the priming of Nrf2 transcription and NF-kB inhibition.
Tolerance to diverse exposures is also essential for human survival. For instance, various exposome and hormesis stimulate changes in the microbiome that lead to increased microbiome diversification. Research has shown that increased diversity of the microbiome is linked to better health outcomes and tolerance to diseases. Reducing the variety of exposome preconditioning can lead to less diversification and leave the host vulnerable to opportunistic pathogens and inappropriate immune responses. Therefore, exposome-shaped biological shields crucially determine host tolerance, diversity, and vulnerability through adaptive hormesis responses.
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