Bacterial Extracellular Vesicles: The Cross-Kingdom Messengers Linking Dietary Phytochemicals, Gut Microbiota, and Host Health

The health-promoting potential of dietary phytochemicals is frequently limited by their low bioavailability, creating a Bioavailability Paradox between limited absorption and systemic health effects. This review introduces the Phytochemical – Microbiota – Bacterial Extracellular Vesicles (BEVs) axis as a conceptual framework. We propose a paradigm shift where the gut microbiota functions as an endogenous bio-manufacturing factory, metabolizing phytochemicals into bioactive intermediates and encapsulating them into BEVs. These biogenically derived EVs serve as stable cross-kingdom messengers that protect their cargo from degradation and utilize transcytosis to bypass intestinal barriers. Once in the bloodstream, they deliver therapeutic agents to distal organs, modulating inflammation and metabolism through the gut-liver and gut-brain axes. By exploring this natural encapsulation process, we highlight the translational potential of BEVs as next-generation nanocarriers for precision nutrition in managing gastrointestinal diseases.