The cost of diet-related chronic disease may soon exceed $1 trillion per year in the United States (JAMA, 2017, v317, p1755), driving the need to understand the dose-response relationships among food components and chronic disease, and establish scientifically-grounded guidance for optimal dietary intakes. To achieve this goal, scientific and methodological transformations are needed: 1) to quantify comprehensively the dynamics of physiological systems, their decay with age, and their response to individual nutrient concentrations, 2) to understand the role of nutrients and the dynamic ranges of their interactions in biological networks in health and disease, and 3) to identify robust biomarkers of nutrient intake, status, function, and their connection to biomarkers of disease.
Chronic diseases are complex traits that manifest over a lifetime. They can originate early in human development through fetal genome programming in response to in utero nutrient exposures and propagate through aging. Aging and age-related chronic disease are manifest by the decay of system networks, and by failure to maintain an adequate number and quality of stem cells throughout life. Hence, biomarkers of chronic disease are linked closely to biomarkers of aging. Identifying age-related changes in the genome that distinguish healthy aging and age-related chronic disease holds the promise of revealing the role of diets and nutrients in modifying and perhaps reversing disease trajectories.
The goal of precision nutrition is to optimize nutrient exposures to achieve healthy human physiological systems. This requires a systems-level understanding of human physiological networks, their placidity, variations in response to nutrient exposures, and the ability to classify population subgroups with respect to their nutritional needs. The diet-disease relationship is highly heterogeneous among individuals, due to differences in genetics, epigenetics, the microbiome, as well as various non-nutritive environmental exposures, including exercise. Needed are next generation biomarkers of nutrition and chronic disease that can classify individuals who are at risk of diet-related chronic disease, and that quantify the dose-response relationships among individual or groups of interacting nutrients in disease onset and progression.
Biochemical reactions integrate upstream genetic, regulatory and environmental conditions to establish organism-wide homeostasis, which may be highly specific for an individual and their current health state. Metabolites also function as signaling molecules through feedback loops that regulate genome expression, stability and epigenetic programming of stem cells. Absolute metabolite levels constitute a fingerprint of the current health and disease state of an organism, whereas metabolic flux data represents the outcome of all regulatory, environmental and thermodynamic events present in a living system. Recent technological innovations in microfluidics allow inexpensive point-of-care assessment of metabolite levels, and in stable-isotope methodologies permit quantitative profiling of the system dynamics of metabolism as turn-over rates of metabolites or metabolic fluxes through pathways. Computational approaches are key to integrate heterogeneous omics data, leading to comprehensive readouts of system functioning that predict occurrence of disease states, as well as inform pharmacological and/or nutrition regimes for health, chronic disease treatment and prevention.
This 4-day meeting brings together experts in nutrition, metabolomics, systems biology, and computer science who otherwise would not interact to advance our fundamental understanding of biological networks, their dynamics, changes with age and interactions with nutrients. Importantly, this meeting will also encourage future research to identify next generation biomarkers for assessment of nutrient needs in health and disease.