Nutrigenomics: integrating genomic approaches into nutrition research

It has been suggested that the supermarket of today will be the pharmacy of tomorrow. Such statements have been derived from recognition of our increasing ability to optimize nutrition, and maintain a state of good health through longer periods of life. The new field of nutrigenomics, which focuses on the interaction between bioactive dietary components and the genome, recognizes that current nutritional guidelines may be ideal for only a relatively small proportion of the population. There is good evidence that nutrition has significant influences on the expression of genes, and, likewise, genetic variation can have a significant effect on food intake, metabolic response to food, individual nutrient requirements, food safety, and the efficacy of disease-protective dietary factors. For example, a significant number of human studies in various areas are increasing the evidence for interactions between single nucleotide polymorphisms (SNPs) in various genes and the metabolic response to diet, including the risk of obesity. Many of the same genetic polymorphisms and dietary patterns that influence obesity or cardiovascular disease also affect cancer, since overweight individuals are at increased risk of cancer development. The control of food intake is profoundly affected by polymorphisms either in genes encoding taste receptors or in genes encoding a number of peripheral signaling peptides such as insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. Total dietary intake, and the satiety value of various foods, will profoundly influence the effects of these genes. Identifying key SNPs that are likely to influence the health of an individual provides an approach to understanding and, ultimately, to optimizing nutrition at the population or individual level. Traditional methods for identification of SNPs may involve consideration of individual variants, using methodologies such as restriction fragment length polymorphisms or quantitative real-time PCR assays. New developments allow identification of up to 500,000 SNPs in an individual, and with increasingly lowered pricings these developments may explode the population-level potential for dietary optimization based on nutrigenomic approaches.     

Ethical, legal and social issues in nutrigenomics: the challenges of regulating service delivery and building health professional capacity

Nutrigenomics, the conjunction of molecular nutrition with human genomics, is among the first publicly available applications of the human genome project. Nutrigenomics raises ethical, legal and social issues particularly with respect to how the public may access nutrigenetic tests and associated nutritional and lifestyle advice. Current regulatory controversy focuses on potential harms associated with direct-to-consumer (DTC) marketing of nutrigenetic tests and especially the need to protect consumers from unreliable tests, false claims and unproven dietary supplements. Nutrigenomics does, however, offer the potential of important health benefits for some individuals. The regulation of nutrigenomic services is slowly evolving, but there is little indication of increased professional capacity to support service delivery. Primary care physicians have minimal training in nutrition and genetics, and medical geneticists are in high demand and short supply. Dietetic practitioners are experts in nutrition science and interest in nutrigenomics is growing among members of this professional group. However, as with physicians, dietetics practitioners would require considerable training to bring nutrigenomics into their practice capacity. A downside of regulatory restrictions on direct consumer access to nutrigenomics companies is that responsible businesses may be hindered in meeting emergent public demand while health care professional groups have not yet developed capacity to provide nutrigenomics services.     

营养基因组学的研究进展

营养学是一门古老的学科, 为人们的健康保护和疾病预防提供了重要的理论指导。随着分子生物学技术的发展, 它已成为21世纪生命科学研究最为主要的技术之一。分子生物学与营养学的结合, 产生了分子营养学。而基因组学与营养学的结合, 则形成了营养基因组学。营养基因组学涵盖了一个广泛的领域, 它研究营养素和基因表达的相互影响, 预测其对营养素的反应。基因组学技术可以帮助确认一些与疾病发生有关的基因, 人们可以根据各自的基因图谱制定一份个性化的饮食方案, 以此防病治病, 使人们的健康状况通过调整饮食来达到最佳。文中重点介绍了营养基因组学的主要研究方法及其应用。     

The challenges for molecular nutrition research 3: comparative nutrigenomics research as a basis for entering the systems level

Human nutrition and metabolism may serve as the paradigm for the complex interplay of the genome with its environment. The concept of nutrigenomics now enables science with new tools and comprehensive analytical techniques to investigate this interaction at all levels of the complexity of the organism. Moreover, nutrigenomics seeks to better define the homeostatic control mechanisms, identify the de-regulation in the early phases of diet-related diseases, and attempts to assess to what extent an individual's sensitizing genotype contributes to the overall health or disease state. In a comparative approach nutrigenomics uses biological systems of increasing complexity from yeast to mammalian models to define the general rules of metabolic and genetic mechanisms in adaptations to the nutritional environment. Powerful information technology, bioinformatics and knowledge management tools as well as new mathematical and computational approaches now make it possible to study these molecular mechanisms at the cellular, organ and whole organism level and take it on to modeling the processes in a "systems biology" approach. This review summarizes some of the concepts of a comparative approach to nutrigenomics research, identifies current lacks and proposes a concerted scientific effort to create the basis for nutritional systems biology.     

Nutrients: the environmental regulation of cardiovascular gene expression

The complexity of nutrient-gene interactions has led to the development of a new branch in the nutrition sciences, the nutrigenomics. The individual susceptibility to nutrients based on environment --> genotype --> phenotype interplay makes this new research field extremely promising although complex. In this review, we highlight and examine recent findings and the most relevant hypotheses on the role of the diet in the onset and progression of cardiovascular diseases. The effect of unbalanced diets on the cardiovascular system is considered one of the most important risk factors both for ischemic and degenerative myocardial pathologies. The concept that nutrigenomics could help in improving public and personal health is becoming tangible indicating future directions for basic and applied research in the pathophysiology of cardiovascular disease.     

Harnessing Nutrigenomics: Development of web-based communication, databases, resources, and tools

Nutrient - gene interactions are responsible for maintaining health and preventing or delaying disease. Unbalanced diets for a given genotype lead to chronic diseases such as obesity, diabetes, cardiovascular, and are likely to contribute to increased severity and/or early-onset of many age-related diseases. Many nutrition and many genetic studies still fail to properly include both variables in the design, execution, and analyses of human, laboratory animal, or cell culture experiments. The complexity ofnutrient-gene interactions has led to the realization that strategic international alliances are needed to improve the completeness of nutrigenomic studies - a task beyond the capabilities of a single laboratory team. Eighty-eight researchers from 22 countries recently outlined the issues and challenges for harnessing the nutritional genomics for public and personal health. The next step in the process of forming productive international alliances is the development of a virtual center for organizing collaborations and communications that foster resources sharing, best practices improvements, and creation of databases. We describe here plans and initial efforts of creating the Nutrigenomics Information Portal, a web-based resource for the international nutrigenomics society. This portal aims at becoming the prime source ofinformation and interaction for nutrigenomics scientists through a collaborative effort.     

Nutrigenomics: a case study in the measurement of insect response to nutritional quality

Recent developments in the area of nutrigenomics hold the promise of providing valuable information about the impact of nutrition on a wide range of biochemical parameters by investigating how nutrition alters global gene expression patterns. Our goal is to use a nutrigenomics approach to identify insect molecular markers that could be used as early indicators of insect responses to different nutritional sources. Such molecular markers could be chosen for degree of expression and evaluated for suitability as nutritional biomarkers by examining developmental and generational expression. Ideal markers would be highly expressed, manifested in the first generation within one developmental stage, and consistent over many generations. Our objective for the current study was to illustrate the potential discovery of molecular markers using Perillus bioculatus (F.) (Heteroptera: Pentatomidae), when reared on an optimal vs. suboptimal diet, and analyze the presence of differentially expressed genes resulting from those treatments. In this paper we present preliminary results of microarray and subtractive hybridization experiments that represent the feasibility of using nutrigenomics to assist in analyzing insect responses to nutritional changes and dietary quality with the intent of stimulating further studies in this area.     

Considerations for the successful development and launch of personalised nutrigenomic foods

The idea that diet and health are related is not new but the concept of direct nutrient-gene interactions is a new one for the food industry and the public to deal with. The ultimate goal of nutrigenomics is the development of foods that can be matched to individual human genotypes in order to benefit the health of those individuals. This paper discusses how personalised, nutrigenomic foods might be developed. Early results from research into food fractions that have the potential to ameliorate Crohn's disease are presented along with illustrations of candidate foods. Issues covering food customisation, consumer response and the ethics of genetic testing for food selection are also discussed briefly.     

The challenges for molecular nutrition research 2: quantification of the nutritional phenotype

In quantifying the beneficial effect of dietary interventions in healthy subjects, nutrition research meets a number of new challenges. Inter individual variation in biomarker values often is larger than the effect related to the intervention. Healthy subjects have a remarkable capacity to maintain homeostasis, both through direct metabolic regulation, metabolic compensation of altered diets, and effective defence and repair mechanisms in oxidative and inflammatory stress. Processes involved in these regulatory activities essentially different from processes involved in early onset of diet related diseases. So, new concepts and approaches are needed to better quantify the subtle effects possibly achieved by dietary interventions in healthy subjects. Apart from quantification of the genotype and food intake (these are discussed in separate reviews in this series), four major areas of innovation are discussed: the biomarker profile concept, perturbation of homeostasis combined with omics analysis, imaging, modelling and fluxes. All of these areas contribute to a better understanding and quantification of the nutritional phenotype.     

Nutritional genomics era: opportunities toward a genome-tailored nutritional regimen

There is increasing evidence indicating that nutritional genomics represents a promise to improve public health. This goal will be reached by highlighting the mechanisms through which diet can reduce the risk of monogenic and common polygenic diseases. Indeed, nutrition is a very relevant environmental factor involved in the development and progression of metabolic disorders, as well as other kind of diseases. The revolutionary changes in the field of genomics have led to the development and implementation of new technologies and molecular tools. These technologies have a useful application in the nutritional sciences, since they allow a more precise and accurate analysis of biochemical alterations, in addition to filling fundamental gaps in the knowledge of nutrient–genome interactions in both health and disease. Overall, these advances will open undiscovered ways in genome-customized diets for disease prevention and therapy. This review summarizes the recent knowledge concerning this novel nutritional approach, paying attention to the human genome variations, such as single-nucleotide polymorphisms and copy number variations, gene expression and innovative molecular tools to reveal them.     

The genetics underlying metabolic signatures in a brown rice diversity panel and their vital role in human nutrition

Brown rice (Oryza sativa) possesses various nutritionally dense bioactive phytochemicals exhibiting a wide range of antioxidant, anti-cancer, and anti-diabetic properties known to promote various human health benefits. However, despite the wide claims made about the importance of brown rice for human nutrition the underlying metabolic diversity has not been systematically explored. Non-targeted metabolite profiling of developing and mature seeds of a diverse genetic panel of 320 rice cultivars allowed quantification of 117 metabolites. The metabolite genome-wide association study (mGWAS) detected genetic variants influencing diverse metabolic targets in developing and mature seeds. We further interlinked genetic variants on chromosome 7 (6.06–6.43 Mb region) with complex epistatic genetic interactions impacting multi-dimensional nutritional targets, including complex carbohydrate starch quality, the glycemic index, antioxidant catechin, and rice grain color. Through this nutrigenomics approach rare gene bank accessions possessing genetic variants in bHLH and IPT5 genes were identified through haplotype enrichment. These variants were associated with a low glycemic index, higher catechin levels, elevated total flavonoid contents, and heightened antioxidant activity in the whole grain with elevated anti-cancer properties being confirmed in cancer cell lines. This multi-disciplinary nutrigenomics approach thus allowed us to discover the genetic basis of human health-conferring diversity in the metabolome of brown rice.     

Methods in Primate Nutritional Ecology: A User’s Guide

An important goal of primatology is to identify the ecological factors that affect primate abundance, diversity, demography, and social behavior. Understanding the nutritional needs of primates is central to understanding primate ecology because adequate nutrition is a prerequisite for successful reproduction. Here, we review nutritional methods and provide practical guidelines to measure nutrient intake by primates in field settings. We begin with an assessment of how to estimate food intake by primates using behavioral observations. We then describe how to collect, prepare, and preserve food samples. Finally, we suggest appropriate nutritional assays for estimating diet nutritional quality and point to the merits and limitations of each. We hope this review will inspire primatologists to use nutritional ecology to answer many unresolved questions in primatology.     

Nutrigenomics: goals and strategies

Nutrigenomics is the application of high-throughput genomics tools in nutrition research. Applied wisely, it will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phase of a diet-related disease and to what extent individual sensitizing genotypes contribute to such diseases. Ultimately, nutrigenomics will allow effective dietary-intervention strategies to recover normal homeostasis and to prevent diet-related diseases.     

Nutritional metabonomics: applications and perspectives

Nowadays, nutrition focuses on improving health of individuals through diet. Current nutritional research aims at health promotion, disease prevention, and performance improvement. Modern analytical platforms allow the simultaneous measurement of multiple metabolites providing new insights in the understanding of the functionalities of cells and whole organisms. Metabonomics, "the quantitative measurement of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic modifications", provides a systems approach to understanding global metabolic regulations of organisms. This concept has arisen from various applications of NMR and MS spectroscopies to study the multicomponent metabolic composition of biological fluids, cells, and tissues. The generated metabolic profiles are processed by multivariate statistics to maximize the recovery of information to be correlated with well-determined stimuli such as dietary intervention or with any phenotypic data or diet habits. Metabonomics is thus uniquely suited to assess metabolic responses to deficiencies or excesses of nutrients and bioactive components. Furthermore, metabonomics is used to characterize the metabolic phenotype of individuals integrating genetic polymorphism, metabolic interactions with commensal and symbiotic partners such as gut microflora, as well as environmental and behavioral factors including dietary preferences. This paper reports several experimental key aspects in nutritional metabonomics, reviews its applications employing targeted and holistic approach analysis for the study of the metabolic responses following dietary interventions. It also reports the assessment of intra- and inter-individual variability in animal and human populations. The potentialities of nutritional metabonomics for the discovery of new biomarkers and the characterization of metabolic phenotypes are discussed in a context of their possible utilizations for personalized nutrition to provide health maintenance at the individual level.     

Integrating anticipated nutrigenomics bioscience applications with ethical aspects

Nutrigenomics is a subspecialty of nutrition science which aims to understand how gene-diet interactions influence individuals' response to food, disease susceptibility, and population health. Yet ethical enquiry into this field is being outpaced by nutrigenomics bioscience. The ethical issues surrounding nutrigenomics face the challenges of a rapidly evolving field which bring forward the additional dimension of crossdisciplinary integrative research between social and biomedical sciences. This article outlines the emerging nutrigenomics definitions and concepts and analyzes the existing ethics literature concerning personalized nutrition and presents "points to consider" over ethical issues regarding future nutrigenomics applications. The interest in nutrigenomics coincides with a shift in emphasis in medicine and biosciences toward prevention of future disease susceptibilities rather than treatment of already established disease. Hence, unique ethical issues emerge concerning the extent to which nutrigenomics can alter our relation to food, boundaries between health and disease, and the folklore of medical practice. Nutrigenomics can result in new social values, norms, and responsibilities for both individuals and societies. Nutrigenomics is not only another new application of "-omics" technologies in the context of gene-diet interactions. Nutrigenomics may fundamentally change the way we perceive human illness while shifting the focus and broadening the scope of health interventions from patients to healthy individuals. In resource- and time-limited healthcare settings, this creates unique ethical dilemmas and distributive justice issues. Ethical aspects of nutrigenomics applications should be addressed proactively, as this new science develops and increasingly coalesces with other applications of genomics in medicine and public health.     

Pregnancy Requires Major Changes in the Quality of the Diet for Nutritional Adequacy: Simulations in the French and the United States Populations

Background

Maternal nutrition is critical to the health of both mother and offspring, but there is a paucity of data on the nutritional adequacy of diets during pregnancy.

Objective

Our objective was to identify to what extent pregnancy reduces the nutritional adequacy of the expecting mother’s diet and if this nutritional gap can be resolved by simple quantitative or qualitative changes in the diet.

Materials and Methods

We evaluated the observed overall nutritional adequacy of diets of French and American women of childbearing age participating in ENNS (n = 344) and NHANES (n = 563) using the probabilistic approach of the PANDiet system, resulting in a 100-point score. Then, we simulated the changes in the PANDiet scores of women of childbearing age who would remain on their diet during pregnancy. Finally, by either increasing the quantity of consumed foods or using eleven snacks recommended during pregnancy, we simulated the effect of a 150-kcal increase in the energy intake of French women.

Results

Observed PANDiet scores were equal to 59.3 ± 7.0 and 58.8 ± 9.3 points respectively in France and in the US. Simulation of pregnancy for women of childbearing age led to a decrease in nutritional adequacy for key nutrients during pregnancy and resulted in reducing PANDiet scores by 3.3 ± 0.1 and 3.7 ± 0.1 points in France and in the US. Simulated 150-kcal increases in energy intake proved to be only partially effective in filling the gap both when the quantity of food consumed was increased and when recommended snacks were used.

Conclusions

The decrease in nutritional adequacy induced by pregnancy cannot be addressed by simply following generic dietary guidelines.     

Human nutrition and food research: opportunities and challenges in the post-genomic era

Sequencing of the human genome has opened the door to the most exciting new era for nutritional science. It is now possible to study the underlying mechanisms for diet-health relationships, and in the near future dietary advice (and possibly tailored food products) for promoting optimal health could be provided on an individual basis, in relation to genotype and lifestyle. The role of food in human evolution is briefly reviewed, from palaeolithic times to modern-day hunter-gatherer societies. The aetiology of 'diseases of modern civilization', such as diabetes, heart disease and cancer, and the effect of changes in dietary patterns are discussed. The risk of disease is often associated with common single nucleotide polymorphisms, but the effect is dependent on dietary intake and nutritional status, and is often more apparent in intervention studies employing a metabolic challenge. To understand the link between diet and health, nutritional research must cover a broad range of areas, from molecular to whole body studies, and is an excellent example of integrative biology, requiring a systems biology approach. The annual cost to the National Health Service of diet-related diseases is estimated to be in excess of 15 billion, and although diet is a key component of any preventative strategy, it is not given the prominence it deserves. For example, less than 1% of the pound 1.6 billion budget for coronary heart disease is spent on prevention. The polygenic and multifactorial nature of chronic diseases requires substantial resources but the potential rewards, in terms of quality of life and economics, are enormous. It is timely therefore to consider investing in a long-term coordinated national programme for nutrition research, combining nutritional genomics with established approaches, to improve the health of individuals and of the nation.     

Nutrigenomic Analysis of Diet-Gene Interactions on Functional Supplements for Weight Management

Recent advances in molecular biology combined with the wealth of information generated by the Human Genome Project have fostered the emergence of nutrigenomics, a new discipline in the field of nutritional research. Nutrigenomics may provide the strategies for the development of safe and effective dietary interventions against the obesity epidemic. According to the World Health Organization, more than 60% of the global disease burden will be attributed to chronic disorders associated with obesity by 2020. Meanwhile in the US, the prevalence of obesity has doubled in adults and tripled in children during the past three decades. In this regard, a number of natural dietary supplements and micronutrients have been studied for their potential in weight management. Among these supplements, (–)-hydroxycitric acid (HCA), a natural extract isolated from the dried fruit rind of Garcinia cambogia, and the micronutrient niacin-bound chromium(III) (NBC) have been shown to be safe and efficacious for weight loss. Utilizing cDNA microarrays, we demonstrated for the first time that HCA-supplementation altered the expression of genes involved in lipolytic and adipogenic pathways in adipocytes from obese women and up-regulated the expression of serotonin receptor gene in the abdominal fat of rats. Similarly, we showed that NBC-supplementation up-regulated the expression of myogenic genes while suppressed the expression of genes that are highly expressed in brown adipose tissue in diabetic obese mice. The potential biological mechanisms underlying the observed beneficial effects of these supplements as elucidated by the state-of-the-art nutrigenomic technologies will be systematically discussed in this review.Key Words: Insulin resistance, glucose tolerance factor, supplemental chromium, Garcinia cambogia, (-)-hydroxycitric acid, overweight, obesity, diabetes, cardiovascular disease, nutritional interventions, microarrays, nutrigenomics.