Paolo Riccio, Emilio Jirillo
Food is indispensable for survival, yet it originates from biological matter derived from other living organisms. Food macromolecules are almost always structurally different from those of the host and may therefore be regarded as foreign biological material. This observation leads to what is defined here as the Food Paradox: food sustains life but initially represents non-self biological material. Digestion resolves this paradox by breaking down food macromolecules to universal molecular units compatible with host metabolism. From this perspective, the Food Paradox is proposed as a conceptual framework linking digestion, gut microbiota, intestinal barrier function, and, eventually, chronic inflammatory diseases. Under physiological conditions, digestion transforms foreign biological material into metabolically compatible nutrients, while the intact intestinal barrier prevents microbes, microbial products, and incompletely digested food molecules from entering the systemic circulation. However, imbalanced dietary patterns may alter gut microbiota composition, promote dysbiosis and intestinal inflammation, and impair intestinal barrier integrity. Increased intestinal permeability may allow microbial components and only partially digested food fragments to reach systemic circulation, thereby eventually contributing to systemic chronic low-grade inflammation.