F3-metabolomics: Integrating feed, fluid, and food metabolomics in dairy production

Metabolomics is increasingly recognized as a powerful approach to decode the biochemical complexity of dairy systems. In this review, we propose a novel integrative framework, F3-metabolomics, that systematically connects feed metabolomics (here described as the metabolomic profiling of different feedstuffs), fluid metabolomics (here newly defined as the metabolomic analysis of animal biofluids), and food metabolomics (the characterization of dairy products as a food category). This feed-fluid-food axis could enable researchers to trace the metabolic fate of nutrients, bioactive compounds, and environmental outputs from the ration, through the animal’s systemic metabolism, to the final product. By formally introducing fluid metabolomics as the central analytical node, encompassing saliva, rumen fluid, blood, urine, milk, and feces, we highlight its role as a dynamic interface linking nutritional strategies to phenotypic and compositional outcomes. Anchored in this structured continuum, the F3-metabolomics framework provides a high-throughput basis to explore animal performance, feed efficiency, and product functionality, with a special focus on milk quality parameters. We critically evaluate recent methodological developments across each metabolomic layer, examine integrated case studies, and discuss practical applications in precision livestock farming, sustainability, and food traceability. Finally, we address current challenges in data harmonization, annotation confidence, and multi-omics integration, proposing a roadmap to accelerate the adoption of F3-metabolomics as a next-generation systems-level paradigm for dairy science.