Single-cell omics for nutrition research: an emerging opportunity for human-centric investigations

Manuela Cassotta; Yasmany Armas Diaz; Danila Cianciosi; Bei Yang; Zexiu Qi; Ge Chen; Santos Gracia Villar; Luis Alonso Dzul López; Giuseppe Grosso; José L. Quiles; Jianbo Xiao; Maurizio Battino; Francesca Giampieri

Resumen:

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.