SPONSOR FEATURE SPONSOR FEATURE NESTLÉ RESEARCH: Harnessing the power of epigenetics for targeted nutrition Authors Diet and genomes interact. Because of its contin- products that are nutritious, safe, promote and Martin Kussmann*, Jennifer Dean*, uous and lifelong impact, nutrition might be the maintain health, and prevent disease. With the Rondo P. Middleton†, Peter J. van most important environmental factor for human advent and development of many new technolo- Bladeren* & Johannes le Coutre* health. Molecular nutrition research strives gies, molecular nutrition research has opened to understand this interaction. Nutrigenetics up new doors of understanding – not only con- *Nestlé Research Center, addresses how an individual’s genetic make-up cerning which dietary components may impact 1000 Lausanne 26, Switzerland. leads to a predisposition for nutritional health; an organism’s health, but also how. These new †Nestlé Purina Research, St. Louis, MO, nutrigenomics (encompassing transcriptomics, insights have allowed a greater understanding 63164 USA. proteomics and metabonomics) asks how nutri- of the systems involved at multiple levels, from tion modulates gene expression; and epigenetics whole animal to the cellular and molecular lev- provides insights into a new level of regulation els. Although challenges in this area still remain, involving mechanisms of development, parental the main focus continues to be the improvement gene imprinting and metabolic programming that of health through diet. Modern molecular nutri- are beyond genetic control. tional research aims at health promotion, dis- Tailoring diets and nutrient compositions to the ease prevention, performance improvement and needs of consumer groups that share the same benefit-risk assessment1. health state, life stage or life style is a main goal Nutrition has conventionally been considered of current nutritional research. While there are an integral part of health maintenance and dis- already food products available that address the ease prevention (especially in cultures such as specific requirements and preferences of certain the Chinese), and the science behind this idea groups, these products are based on empirical was based primarily on epidemiological studies. research rather than on genomic or (epi)genetic The task now is to take this foundational research assessment. Genetics and epigenetics build the to the next scientific level – to analyze gene, scientific foundations for understanding human protein and metabolite profiles of individuals in variability in nutritional preference, require- different health and nutritional conditions – to ments, and response to diet; and furthermore, find early signs (biomarkers) that indicate devia- epigenetics may reveal how environmental tions from healthy metabolism and possible tar- influences can alter this variability across the life gets for correcting these deviations by nutritional span. Inspired by the potential for personalized means2. A further objective is to reveal reactions nutrition counseling, epigenetics research may towards different diets at the systemic level to exert a major influence on consumer diagnos- demonstrate nutritional efficacy2. Therefore, tics to promote health maintenance and disease genomics and genetics applied within the con- prevention. text of nutrition and health have the potential to: Modern nutritional research spans from the deliver biomarkers for health status and health discovery of bioactive food ingredients and the effects, reveal early indicators for disease dis- investigation of their bioavailability and bioeffi- position, differentiate dietary responders from cacy, to the assessment of individual dietary needs non-responders, and, last but not least, uncover via genomic and genetic approaches. The present bioactive, beneficial food components1. paper summarizes current findings in the field of epigenetics and gives an outlook on potential Nutrition and genes health benefits and further research needs. Diet and food components are the prime envi- ronmental factors that affect the human genome, Nutrition research in the 21st century transcriptome, proteome and metabolome, and In light of the increasing importance of nutri- this life-long interaction largely defines the health tion in the development, prevention and man- or disease state of an individual. Most, if not all agement of chronic diseases, modern nutrition nutrients have at least indirect effects on gene research faces the challenge to holistically and protein expression and thus, metabolism. understand how dietary components interact While genomics is about expression and genetics with and within cells and organisms; and to use is about the disposition of an organism, epige- this knowledge to develop new strategies and netics is about development and programming. SPONSOR RETAINS SOLE RESPONSIBILITY FOR CONTENT SPONSOR FEATURE Genetics Epigenetics Transcriptomics Proteomics Metabolomics METHYLATED DNA GENERATED DNA RNA PROTEINS HISTONES, RNAi METABOLITES SPONSOR FEATURE CH3 What may be What appears What makes it What has The Blueprint programmed to happen happen happened DIET DIET DIET DIET Figure 1 | Impact of diet on the genome and metabolism Epigenetics represents an emerging set of mecha- in humans, are usually significantly smaller than imprinting, a genetic mechanism that controls nisms revealing how the environment, including pharmacological or toxicological effects. gene expression in a parent-of-origin-specific food and nutrition, constantly shapes and influ- manner4 (i.e. gene expression depends on ences the genome. With a prolonged life span Epigenetics whether an allele is inherited from the mother and changing lifestyles in developed countries, Whereas many earlier studies assumed that or the father). Furthermore, epigenetic regulation chronic diseases have become more prevalent, SNPs (single-nucleotide polymorphisms) were is involved in tissue-specific gene expression and and nutrigenomics, nutrigenetics and epigenet- the main source of human genetic variability, silencing. ics are the key scientific platforms to advance an increasing body of evidence now suggests During early embryogenesis, the mammalian the understanding of health maintenance and that additional layers of variability, including genome is ‘cleared’ of most epigenetic marks, disease prevention through nutrition3. epigenetic regulation, such as DNA methyla- which are then progressively re-established dur- Current nutritional and genetic epidemiologi- tion, are implicated in genetic variation. Many ing embryonic development. The epigenome is cal approaches can be difficult to apply at the complex diseases such as Inflammatory Bowel therefore most vulnerable to environmentally personalized or individual level. These methods Disease (IBD), encompassing Crohn’s Disease induced alterations during embryogenesis, when yield risk factors derived from population studies. and Ulcerative Colitis, are associated with SNPs, DNA synthesis is rapid and the DNA methylation These risk factors are statistical estimates of the particularly in chromosomal regions, but also pattern and chromatin structure is established for percentage of disease reduction in a population, with CNVs (copy number variants) of certain normal development. Once this has been accom- if the risk was to be avoided or the gene variant other genes4. Such discoveries suggest that a plished, these epigenetic alterations are passed was absent. Considering the genetic diversity of detailed description of the genetic background on to the daughter cells during somatic cell divi- human populations, the complexity of foods, of complex diseases is a challenging but nec- sion. Epigenetic marks that are not completely cultures and lifestyles, and the variety of meta- essary objective to better prevent pathological erased during gametogenesis or are not well re- bolic processes, identifying individual risk fac- development of such diseases. established during embryonic development can tors poses enormous challenges for personalizing Epigenetics literally means ‘above genetics’, affect health not only in the present, but also dietary advice. alluding to alterations of genetic material that do in future generations. Additionally, epigenetic Additionally, assessing the metabolic response not affect the DNA sequence itself: this includes marks may be transmitted across generations, to complex foods by Omics applications dif- DNA methylation patterns, chromatin structure either directly through meiosis or indirectly in the fers fundamentally from approaches in which and histone codes, as well as non-coding small next generation through replication of the condi- a single active principle is typically studied RNAs. DNA methylation can be exerted at sus- tions in which the epigenetic change occurred. (such as pharmacology or toxicology). Food ceptible life phases (especially around birth) Individuals have two alleles of most genes. contains macronutrients (carbohydrates, lipids and can be sustained throughout that precise One is inherited from the mother and one from and proteins) and micronutrients (vitamins, life phase, the entire lifespan, or even through the father. When both copies of a gene are active, minerals and trace elements) that exhibit effects the course of several generations. It seems to the system exhibits redundancy and is less sus- at RNA, protein and metabolite levels in a cell provide a mechanism for long-term metabolic ceptible to dysfunction. With imprinted genes, or organism.