Can exosomes transfer the preconditioning effects triggered by (poly)phenol compounds between cells?

Effective strategies in prolonging life- and health span are increasingly recognized as acting as mild stressors. Micronutrients and other dietary compounds such as (poly)phenols may act as moderate stressors and confer protective effects via a preconditioning phenomenon. (Poly)phenols and their metabolites may not need to reach their target cells to produce biologically significant responses, so that cells exposed to it at entry points may communicate signals to other cells. One of such "communication" mechanisms could occur through extracellular vesicles, including exosomes. In vitro loading of exosomes with (poly)phenols has been used to achieve targeted exosome homing. However, it is unknown if similar shuttling phenomena occur in vivo upon (poly)phenols consumption. Alternatively, exposure to (poly)phenols might trigger responses in exposed organs, which can subsequently signal to cells distant from exposure sites via exosomes. The currently available studies favor indirect effects of (poly)phenols, tempting to suggest a "billiard-like" or "domino-like" propagating effect mediated by quantitative and qualitative changes in exosomes triggered by (poly)phenols. In this review, we discuss the limited current data available on how (poly)phenols exposure can potentially modify exosomes activity, highlighting major questions regarding how (epi)genetic, physiological, and gut microbiota factors can modulate and be modulated by the putative exosome-(poly)phenolic compound interplay that still remains to be fully understood.