Rewiring nutrition: Chemical insights into the physiological and microbiological roles of food's microconstituents

Abstract The expanding field of nutritional science increasingly recognizes food‐derived microconstituents as critical modulators of human health beyond their classical nutritional roles. This review provided a comprehensive and mechanistically grounded synthesis of the chemical diversity, molecular mechanisms, microbiome‐mediated transformations, and translational applications of dietary microconstituents, including polyphenols, bioactive peptides, terpenoids, sulfur‐containing compounds, and non‐digestible oligosaccharides. Integrating advances in analytical chemistry, systems biology, and microbiome research, it elucidates how these compounds regulate key physiological processes, including oxidative stress, inflammation, metabolic homeostasis, epigenetic modulation, and neuroimmune signaling. A central aim is to bridge the gap between molecular insights and practical nutritional applications by incorporating emerging tools such as multi‐omics technologies, artificial intelligence (AI), and advanced experimental platforms, including gut‐on‐chip and organoid systems. Particular emphasis is placed on the bidirectional interactions between dietary microconstituents and the gut microbiota, highlighting microbial biotransformation as a determinant of bioavailability and bioactivity through modulation of signaling pathways such as Nrf2, NF‐κB, AMPK, mTOR, and SIRT1. The novelty of this review lies in its integrative, systems‐level framework linking chemical structure–activity relationships with microbiome dynamics and host physiology, advancing beyond descriptive approaches toward predictive nutrition models. Key research gaps are critically addressed, including inter‐individual variability, limited bioavailability, lack of standardized biomarkers, and insufficient consideration of food matrix–microbiome interactions. Future perspectives emphasize omics‐integrated longitudinal studies, AI‐driven predictive modeling, regulatory harmonization, and sustainable recovery of bioactive compounds within circular bioeconomy frameworks. Collectively, this review advances a microbiome‐integrated and AI‐enabled paradigm for precision nutrition and next‐generation functional food development.