Diet–Immune Crosstalk: Plant-Derived Bioactives Shaping Immunity in Metabolic Disease and Cancer

Diet and plant-derived bioactives are now recognized as active regulators of immune tone that link chronic metabolic dysfunction to cancer initiation, progression, and therapy response. As 2025 closes, advances in single-cell and spatial profiling, high-resolution metabolomics, and microbiome–metabolite analytics are revealing how phytochemicals and dietary patterns reshape innate and adaptive immunity through immunometabolic checkpoints. Emerging evidence highlights roles for polyphenols, flavonoids, carotenoids, terpenoids, alkaloids, lignans, fibers, and bioactive lipids, often via microbiome transformation, modulating macrophage polarization and lipid handling, T cell metabolic fitness and exhaustion, Treg/Th17 balance, NK cell function, and trained immunity. Concurrently, nutrition intervention trials increasingly include immune endpoints, and early signals suggest potential synergy (or interference) with metabolic therapies and cancer immunotherapies. However, key gaps remain around causality, dose–response, bioavailability and formulation, population diversity, and reproducibility, limiting translation into precision nutrition strategies for metabolic disease and oncology.The central goal of this Research Topic is to elucidate, quantify, and translate how diet- and plant-derived bioactives shape immune responses relevant to metabolic disease and cancer. By integrating mechanistic immunology with human nutrition science and multi-omics, we aim to define actionable pathways, biomarkers, and interventions that can inform prevention, risk modification, adjuvant strategies, and survivorship care. We particularly encourage work that connects dietary exposures to immune remodeling through the microbiome–metabolite–host axis and evaluates clinical relevance, including interactions with standard metabolic agents and cancer therapies.We welcome Original Research, Reviews, Mini-Reviews, Methods, Brief Reports, Perspectives, and Opinion manuscripts addressing, but not limited to:• Molecular and cellular programs modulated by plant bioactives: macrophage inflammation and lipid metabolism; T cell exhaustion/metabolic fitness; Treg/Th17 balance; NK cytotoxicity; innate training and inflammasome activity.• Diet–microbiome–metabolite–immune interactions: short-chain fatty acids; bile acid–FXR/TGR5 signaling; tryptophan–indole–AhR pathways; microbial biotransformation of polyphenols and fibers.• Disease contexts: obesity, insulin resistance/T2D, NAFLD/NASH, atherosclerosis; tumor initiation, microenvironment remodeling, metastasis, and therapy resistance.• Clinical and community-based trials with immune endpoints; synergy or interference with immunotherapies and metabolic/endocrine agents.• Precision nutrition and causal inference: nutrigenomics/epigenomics, metabolomics/lipidomics, single-cell and spatial profiling; Mendelian randomization, target trial emulation.• Translation and equity: bioavailability/formulations (whole foods vs extracts), dose–response and safety, population diversity and dietary patterns, reporting standards and reproducibility. Topic editors: Aishwarya Jala, Farid Khallouki Source: https://www.frontiersin.org/research-topics/75902/diet-immune-crosstalk-plant-derived-bioactives-shaping-immunity-in-metabolic-disease-and-cancer