Bioactive compounds found in edible plants and foods are vital for human and planetary health, yet their significance remains underappreciated. These natural bioactives, as part of whole diets, ingredients, or supplements, can modulate multiple aspects of human health and wellness. Recent advancements in omic sciences and computational biology, combined with the development of Precision Nutrition, have contributed to the convergence of nutrition and medicine, as well as more efficient and affordable healthcare solutions that harness the power of food for prevention and therapy. Innovation in this field is crucial to feed a growing global population sustainably and healthily. This requires significant changes in our food system, spanning agriculture, production, distribution and consumption. As we are facing pressing planetary health challenges, investing in bioactive-based solutions is an opportunity to protect biodiversity and the health of our soils, waters, and the atmosphere, while also creating value for consumers, patients, communities, and stakeholders. Such research and innovation targets include alternative proteins, such as cellular agriculture and plant-derived protein; natural extracts that improve shelf-life as natural preservatives; upcycling of agricultural by-products to reduce food waste; and the development of natural alternatives to synthetic fertilizers and pesticides. Translational research and innovation in the field of natural bioactives are currently being developed at two levels, using a systems-oriented approach. First, at the biological level, the interplay between these compounds and the human host and microbiome is being elucidated through omics research, big data and artificial intelligence, to accelerate both discovery and validation. Second, at the ecosystem level, efforts are focused on producing diverse nutrient-rich, flavorful, and resilient, yet high-yield agricultural crops, and educating consumers to make informed choices that benefit both their health and the planet. Adopting a system-oriented perspective helps: unravel the intricate and dynamic relationships between bioactives, nutrition, and sustainability outcomes, harnessing the power of nature to promote human health and wellbeing; foster sustainable agriculture and protect the ecosystem. Interdisciplinary collaboration in this field is needed for a new era of research and development of practical food-based solutions for some of the most pressing challenges humanity and our planet are facing today.

Nature has the answer to many of our questions about human health. Natural bioactives, especially when derived from sustainable plant and food sources, provide a plethora of molecular solutions to nutritionally actionable, chronic conditions. The spectrum of these conditions, such as metabolic, immune, and gastrointestinal disorders, has changed with prolonged human life span, which should be matched with an appropriately extended health span: “adding years to life and adding life to years”. Natural bioactives can be classified into micronutrients (i.e., vitamins, and minerals), phytonutrients, bioactive peptides,and pre-, pro-, post- and synbiotics. Bioactives act in concert and interact with the human host and its (gut) microbiome. Therefore, the future of translational science on natural bioactives is being built on a: (a) systems-level rather than reductionist approaches to understanding their interdependent, and at times additive functions, as well as their interactions with the human host and (gut) microbiome; and (b) the leverage of artificial intelligence for discovery and validation, thereby substantially reducing the time from idea and concept to finished solutions for consumers and patients. Rather than focusing on a particular class of bioactive food molecules, as often done in molecular food and nutrition articles, this review embraces a broad range of these bioactives and puts them into perspective regarding a more efficient and sustainable leverage of the biochemical richness of plants and foods for its diverse positive effects on human health.Keywords: bioactive, micronutrient, phytonutrient, prebiotic, probiotic, synbiotic, peptide, artificial intelligence, discovery, validation