02547nas a2200301 4500000000100000000000100001008004100002653001500043653003500058653001800093653001600111653002300127653001800150100002100168700002800189700002400217700002300241700002400264700001500288700001300303700002000316700002100336245007400357856006300431490000800494520172900502022001402231 d10aOne Health10aalternatives to animal testing10aEcotoxicology10afood safety10anutrition research10aorgan-on-chip1 aManuela Cassotta1 aMaria Elexpuru-Zabaleta1 aSandra Sumalla Cano1 aYasmany Armas Diaz1 aFrancesca Giampieri1 aZou Xiaobo1 aDi Zhang1 aGiuseppe Grosso1 aMaurizio Battino00aOrgan-on-Chip: The Future of Nutrition Research in a One Health World uhttps://onlinelibrary.wiley.com/doi/abs/10.1002/fft2.700000 vn/a3 aThe One Health approach emphasizes the interconnectedness of human, animal, and environmental health, recognizing that the health of each is interdependent and influenced by shared ecosystems. Nutrition research plays a critical role in improving health outcomes across these domains, with implications for sustainability and food security. Organ-on-chip (OoC) technologies have emerged as innovative tools replicating key organ functions, supporting disease modeling, drug discovery, and personalized medicine. They also hold promise as alternatives to traditional animal models. This systematic review examines the potential of OoC technologies within the One Health framework and nutrition research, focusing on (1) their ability to replicate human and animal organ functions, (2) applications in food safety and ecotoxicology, and (3) their use in studying food components’ health effects. Challenges and future directions for adoption are also discussed. Although fully replicating the complexity of in vivo physiology remains a challenge, OoCs offer a promising platform to simulate organ functions and interactions. These systems hold significant potential for advancing food safety assessments, studying food impacts on health, and addressing sustainability in food systems. Challenges such as standardization, scalability, accessibility, and biases toward traditional models remain. Despite these hurdles, current advancements underscore the versatility and promise of OoCs, positioning them as valuable tools for driving innovation in nutrition research, food and feed safety, and ecotoxicology. With continued progress, OoCs are poised to make significant contributions to the goals of the One Health framework. a2643-8429