%A Manuela Cassotta %A Yasmany Armas Diaz %A Danila Cianciosi %A Bei Yang %A Zexiu Qi %A Ge Chen %A Santos Gracia Villar %A Luis Alonso Dzul López %A Giuseppe Grosso %A José L. Quiles %A Jianbo Xiao %A Maurizio Battino %A Francesca Giampieri %R doi:10.1080/10408398.2025.2566387 %T Single-cell omics for nutrition research: an emerging opportunity for human-centric investigations %D 2025 %K Nutrition research; organoids; personalized nutrition; 3Rs; single-cell omics %J Critical Reviews in Food Science and Nutrition %P 1-15 %X Understanding how dietary compounds affect human health is challenged by their molecular complexity and cell-type–specific effects. Conventional multi-cell type (bulk) analyses obscure cellular heterogeneity, while animal and standard in vitro models often fail to replicate human physiology. Single-cell omics technologies—such as single-cell RNA sequencing, as well as single-cell–resolved proteomic and metabolomic approaches—enable high-resolution investigation of nutrient–cell interactions and reveal mechanisms at a single-cell resolution. When combined with advanced human-derived in vitro systems like organoids and organ-on-chip platforms, they support mechanistic studies in physiologically relevant contexts. This review outlines emerging applications of single-cell omics in nutrition research, emphasizing their potential to uncover cell-specific dietary responses, identify nutrient-sensitive pathways, and capture interindividual variability. It also discusses key challenges—including technical limitations, model selection, and institutional biases—and identifies strategic directions to facilitate broader adoption in the field. Collectively, single-cell omics offer a transformative framework to advance human-centric nutrition research. %L uniromana17867