Xenohormesis: sensing the chemical cues of other species

Abstract

Many plant molecules interact with and modulate key regulators of mammalian physiology in ways that are beneficial to health, but why? We propose that heterotrophs (animals and fungi) are able to sense chemical cues synthesized by plants and other autotrophs in response to stress. These cues provide advance warning about deteriorating environmental conditions, allowing the heterotrophs to prepare for adversity while conditions are still favorable.

Figure 1. Direct Modulation of Key Mammalian Enzymes by Plant Metabolites

A surprising number of plant molecules in our diet interact with key regulators of mammalian physiology to provide health benefits. Shown are three examples: resveratrol found in numerous plants and concentrated in red wine; curcumin from turmeric; and epigallocatechin-3-gallate (EGCG) in green tea. These compounds modulate key pathways that control inflammation, the energy status of cells, and cellular stress responses in a way that is predicted to increase health and survival of the organism. Such observations raise the question, are these biochemical interactions merely a remnant of what existed in the common ancestor of plants and animals, or is selection maintaining interactions between the molecules of plants and animals? Some interactions activate signaling pathways (arrows) whereas others inhibit them (bars). Solid arrows or bars indicate instances where there is some evidence of a direct interaction of the plant metabolite with a mammalian protein.

Figure 2. The Xenohormesis Hypothesis

We propose that the common ancestor of plants and animals synthesized polyphenols. Since the divergence of phyla, there has been selection such that heterotrophs (animals and fungi) detect chemical cues about their environment from plants and other autotrophs (that is, organisms that derive energy from light or inorganic chemical reactions). These chemical cues would give the heterotroph advance warning about the deterioration of the environment, allowing them to prepare while conditions are still relatively favorable. The theory predicts that many key mammalian enzymes and receptors will have evolved binding pockets that allow modulation by molecules produced by other species.