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.     

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.     

Current perspectives in avian nutrition: domestic animal models and their role in conservation management

As biodiversity declines, wildlife conservation focuses on in situ and ex situ management strategies. Zoo-based breeding programmes are often designed to contribute to the conservation of species that are threatened in the wild. Diet contributes to the reproductive success, disease status and longevity of all animals. It is near-impossible to replicate a species' diet in captivity using only the species they consume in the wild, but the nutritional composition of a wild diet, if known, can be closely matched using commercially available foods for which the nutritional composition has been calculated. Ecological research has identified food items of importance in the diet of many species. However, the nutritional composition of these food items is rarely evaluated, even though the composition of wild food items is important in understanding the dietary adaptations and requirements of wildlife. In contrast, the nutritional requirements of domestic species are well researched and can be used to predict a range of plausible nutrient requirements of some wild species, especially those with similar life histories. Access to wild populations provides further opportunities for nutritional science to determine the requirements of individual species. Small-scale dietary experimentation undertaken at conservation institutions may show positive effects on health and welfare but is rarely published in the scientific literature. This review describes current standards in nutritional management of birds and recommends pathways for filling knowledge gaps. Research on mammals has dominated the nutrition literature, so there is a relative lack of nutritional management information for birds. We combine concepts of domestic animal nutrition with recent findings on the nutritional requirements of birds to provide a foundation for further studies of avian nutrition. We call for the broader zoological community to share data and collaborate on nutritional research to support conservation institutions in nutritional management of wild birds.     

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.     

Contributions of nutrition science to anthropological research.

Certain investigations of nutrition scientists have demonstrated the effects of cultural practices on nutrient intake. Anthropologists, too, have studied diets and food-related behavior, although until recently their interests infrequently included nutritional status. In the last decade, nutrition scientists' research helped stimulate the creation of an interdisciplinary specialty, nutritional anthropology, that combines techniques from both nutritional and anthropological science in the study of food use in relation to health. Practitioners of this expanding field make useful contributions to research in human nutrition through study of social aspects of the diet of individuals and groups. Their assistance can be particularly helpful in studies of populations in developing countries and of ethnic minorities in this country. Certain unanswered nutritional questions, which might more readily be solved by the combined efforts of nutritionists and nutritional anthropologists than by either professional alone, are presented.     

Do we know enough? A scientific and ethical analysis of the basis for genetic-based personalized nutrition

This article discusses the prospects and limitations of the scientific basis for offering personalized nutrition advice based upon individual genetic information. Two divergent scientific positions are presented, with an ethical comment. The crucial question is whether the current knowledge base is sufficiently strong for taking an ethically responsible decision to offer personalized nutrition advice based upon gene–diet–health interaction. According to the first position, the evidence base for translating the outcomes of nutrigenomics research into personalized nutritional advice is as yet immature. There is also limited evidence that genotype-based dietary advice will motivate appropriate behavior changes. Filling the gaps in our knowledge will require larger and better randomized controlled trials. According to the second position, personalized nutrition must be evaluated in relation to generally accepted standard dietary advice—partly derived from epidemiological observations and usually not proven by clinical trials. With personalized nutrition, we cannot demand stronger evidence. In several specific cases of gene–diet interaction, it may be more beneficial for individuals with specific genotypes to follow personalized advice rather than general dietary recommendations. The ethical comment, finally, considers the ethical aspects of deciding how to proceed in the face of such uncertainty. Two approaches for an ethically responsible way forward are proposed. Arguing from a precautionary approach, it is suggested that personalized dietary advice should be offered only when there is strong scientific evidence for health effects, followed by stepwise evaluation of unforeseen behavioral and psychological effects. Arguing from theoretical and applied ethics as well as psychology, it is also suggested that personalized advice should avoid paternalism and instead focus on supporting the autonomous choice of each person.     

Protein synthesis in crustaceans: a review focused on feeding and nutrition

This review aimed to place crustacean research on in vivo protein synthesis into a broader context, assess its potential for providing further insights into crustacean nutrition and physiology, and recommend future directions relevant to crustacean aquaculture. In crustaceans the flooding dose measurement of protein synthesis is the only method that has been used, it is relatively complex, time consuming and uses radioactive labels. Protein synthesis provides a subtle approach to assessing imbalances and deficiencies in dietary amino acid and energy. In addition, the calculation of protein synthesis retention efficiency (SRE) is recommended in order to understand and optimize parameters such as feeding regime and diet composition. For prawns, SRE was highest at optimum dietary protein content and quality. Similarly the most efficient feeding regimes in juvenile lobsters were demonstrated by the highest efficiency of retaining synthesized protein. Understanding how various abiotic and biotic factors influence protein synthesis has great potential for improving different aspects of crustacean aquaculture but very few studies have done this; better knowledge of how abiotic and biotic factors affect crustacean protein synthesis will contribute to optimising growth of crustaceans in culture.     

The genome revolution and its role in understanding complex diseases

The completion of the human genome sequence in 2003 clearly marked the beginning of a new era for biomedical research. It spurred technological progress that was unprecedented in the life sciences, including the development of high-throughput technologies to detect genetic variation and gene expression. The study of genetics has become “big data science”. One of the current goals of genetic research is to use genomic information to further our understanding of common complex diseases. An essential first step made towards this goal was by the identification of thousands of single nucleotide polymorphisms showing robust association with hundreds of different traits and diseases. As insight into common genetic variation has expanded enormously and the technology to identify more rare variation has become available, we can utilize these advances to gain a better understanding of disease etiology. This will lead to developments in personalized medicine and P4 healthcare. Here, we review some of the historical events and perspectives before and after the completion of the human genome sequence. We also describe the success of large-scale genetic association studies and how these are expected to yield more insight into complex disorders. We show how we can now combine gene-oriented research and systems-based approaches to develop more complex models to help explain the etiology of common diseases. This article is part of a Special Issue entitled: From Genome to Function.     

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。     

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.     

Ethical issues raised by personalized nutrition based on genetic information

Four principles are taken as basis for the ethical analysis: autonomy, nonmaleficence, beneficence, and justice. Health is understood as a limited aspect of wellbeing. Food is understood as an important aspect of wellbeing, not only an instrument for health. Modern society is characterized by a tendency to identify wellbeing with external rather than subjective circumstances, to identify wellbeing with health, and to create exaggerated health expectations. Based upon this understanding, aspects of personalized nutrition are discussed: genetic testing, counselling, and development of special dietary products. Today the predictive value of genetic tests for personal nutrition is limited, and experimental at best. Recommendations for the future: Personalized nutrition must be based on solid knowledge. Phenotypic analyses should be used when adequate. When a genetic test can have a clear advantage, this should be preferred. Opportunistic screening should only be used when clearly beneficial. Specially trained persons should collect information from genetic tests and carry through councelling on a personal basis. Marketing of genetic tests directly sold to the public should be discouraged. Development of special products for personalized nutrition may be necessary in some cases. However, this may also lead to a medicalization of diet.     

Understanding the nutrigenomic definitions and concepts at the food-genome junction

The marked differences in individual response to dietary factors have led to major controversies in nutrition and puzzled nutrition scientists over the last century. The emerging field of nutrigenomics helps us to understand the basis for some of these differences and also promises us the ability to tailor diet based on individual genetic makeup. Great advances in Human Genome Project, documentation of single nucleotide polymorphisms (SNPs) in candidate genes and their association with metabolic imbalances have gradually added new tests to the nutrigenomic panel. Studies based on ethnopharmacology and phytotherapy concepts showed that nutrients and botanicals can interact with the genome causing marked changes in gene expression. This has led to the commercial development of nutraceuticals and functional foods that can modify negative health effects of individual genetic profile bringing the field to the "food/genome" junction. Despite the promise of nutrigenomics to personalize diet, there is skepticism whether it can truly bring about meaningful modification of the risk factors connected to chronic diseases, due to the lack of large scale nutrition intervention studies. Several intervention studies currently underway in the United States and abroad (Israel, Spain, and France) will further help validate nutrigenomic concepts. France has already introduced a National Nutrition and Health Program to assess nutritional status and risk of major metabolic diseases. As the field(s) related to nutritional genomics advance in their scope, it is essential that: (a) strict guidelines be followed in the nomenclature and definition of the subdisciplines; and (b) the state/federal regulatory guidelines be updated for diagnostic laboratories, especially for those offering tests directly to the public (without a physician's request) to help protect the consumer.     

Plant science and human nutrition: challenges in assessing health-promoting properties of phytochemicals

The rise in noncommunicable chronic diseases associated with changing diet and lifestyles throughout the world is a major challenge for society. It is possible that certain dietary components within plants have roles both in reducing the incidence and progression of these diseases. We critically review the types of evidence used to support the health promoting activities of certain phytochemicals and plant-based foods and summarize the major contributions but also the limitations of epidemiological and observational studies and research with the use of cell and animal models. We stress the need for human intervention studies to provide high-quality evidence for health benefits of dietary components derived from plants.     

Diet and asthma: looking back,moving forward

Asthma is an increasing global health burden, especially in the western world. Public health interventions are sought to lessen its prevalence or severity, and diet and nutrition have been identified as potential factors. With rapid changes in diet being one of the hallmarks of westernization, nutrition may play a key role in affecting the complex genetics and developmental pathophysiology of asthma. The present review investigates hypotheses about hygiene, antioxidants, lipids and other nutrients, food types and dietary patterns, breastfeeding, probiotics and intestinal microbiota, vitamin D, maternal diet, and genetics. Early hypotheses analyzed population level trends and focused on major dietary factors such as antioxidants and lipids. More recently, larger dietary patterns beyond individual nutrients have been investigated such as obesity, fast foods, and the Mediterranean diet. Despite some promising hypotheses and findings, there has been no conclusive evidence about the role of specific nutrients, food types, or dietary patterns past early childhood on asthma prevalence. However, diet has been linked to the development of the fetus and child. Breastfeeding provides immunological protection when the infant''s immune system is immature and a modest protective effect against wheeze in early childhood. Moreover, maternal diet may be a significant factor in the development of the fetal airway and immune system. As asthma is a complex disease of gene-environment interactions, maternal diet may play an epigenetic role in sensitizing fetal airways to respond abnormally to environmental insults. Recent hypotheses show promise in a biological approach in which the effects of dietary factors on individual physiology and immunology are analyzed before expansion into larger population studies. Thus, collaboration is required by various groups in studying this enigma from epidemiologists to geneticists to immunologists. It is now apparent that this multidisciplinary approach is required to move forward and understand the complexity of the interaction of dietary factors and asthma.     

Nutritional psychiatry research: an emerging discipline and its intersection with global urbanization,environmental challenges and the evolutionary mismatch

In 21st-century public health, rapid urbanization and mental health disorders are a growing global concern. The relationship between diet, brain function and the risk of mental disorders has been the subject of intense research in recent years. In this review, we examine some of the potential socioeconomic and environmental challenges detracting from the traditional dietary patterns that might otherwise support positive mental health. In the context of urban expansion, climate change, cultural and technological changes and the global industrialization and ultraprocessing of food, findings related to nutrition and mental health are connected to some of the most pressing issues of our time. The research is also of relevance to matters of biophysiological anthropology. We explore some aspects of a potential evolutionary mismatch between our ancestral past (Paleolithic, Neolithic) and the contemporary nutritional environment. Changes related to dietary acid load, advanced glycation end products and microbiota (via dietary choices and cooking practices) may be of relevance to depression, anxiety and other mental disorders. In particular, the results of emerging studies demonstrate the importance of prenatal and early childhood dietary practices within the developmental origins of health and disease concept. There is still much work to be done before these population studies and their mirrored advances in bench research can provide translation to clinical medicine and public health policy. However, the clear message is that in the midst of a looming global epidemic, we ignore nutrition at our peril.     

Intergenerational effects of nutrition on immunity: a systematic review and meta‐analysis

Diet and immunity are both highly complex processes through which organisms interact with their environment and adapt to variable conditions. Parents that are able to transmit information to their offspring about prevailing environmental conditions have a selective advantage by ‘priming’ the physiology of their offspring. We used a meta‐analytic approach to test the effect of parental diet on offspring immune responses. Using the geometric framework for nutrition (a method for analysing diet compositions wherein food nutrient components are expressed as axes in a Cartesian coordinate space) to define dietary manipulations in terms of their energy and macronutrient compositions, we compiled the results of 226 experiments from 38 published papers on the intergenerational effects of diet on immunity, across a range of study species and immunological responses. We observed intergenerational impacts of parental nutrition on a number of offspring immunological processes, including expression of pro‐inflammatory biomarkers as well as decreases in anti‐inflammatory markers in response to certain parental diets. For example, across our data set as a whole (encompassing several types of dietary manipulation), dietary stress in parents was seen to significantly increase pro‐inflammatory cytokine levels measured in offspring (overall d = 0.575). All studies included in our analysis were from experiments in which the offspring were raised on a normal or control diet, so our findings suggest that a nutrition‐dependent immune state can be inherited, and that this immune state is maintained in the short term, despite offspring returning to an ‘optimal’ diet. We demonstrate how the geometric framework for nutrition can be used to disentangle the role that different forms of dietary manipulation can have on intergenerational immunity. For example, offspring B‐cell responses were significantly decreased when parents were raised on a range of different diets. Similarly, our approach allowed us to show that a parental diet elevated in protein (regardless of energy composition and relative to a control diet) can increase expression of inflammatory markers while decreasing B‐cell‐associated markers. By conducting a systematic review of the literature, we have identified important gaps that impair our understanding of the intergenerational effects of diet, such as a paucity of experimental studies involving increased protein and decreased energy, and a lack of studies directed at the whole‐organism consequences of these processes, such as immune resilience to infection. The results of our analyses inform our understanding of the effects of diet on physiological state across diverse biological fields, including biomedical sciences, maintenance of agricultural breed stock and conservation breeding programs, among others.     

SNP discovery in associating genetic variation with human disease phenotypes

With the completion of the human genome project, attention is now rapidly shifting towards the study of individual genetic variation. The most abundant source of genetic variation in the human genome is represented by single nucleotide polymorphisms (SNPs), which can account for heritable inter-individual differences in complex phenotypes. Identification of SNPs that contribute to susceptibility to common diseases will provide highly accurate diagnostic information that will facilitate early diagnosis, prevention, and treatment of human diseases. Over the past several years, the advancement of increasingly high-throughput and cost-effective methods to discover and measure SNPs has begun to open the door towards this endeavor. Genetic association studies are considered to be an effective approach towards the detection of SNPs with moderate effects, as in most common diseases with complex phenotypes. This requires careful study design, analysis and interpretation. In this review, we discuss genetic association studies and address the prospect for candidate gene association studies, comparing the strengths and weaknesses of indirect and direct study designs. Our focus is on the continuous need for SNP discovery methods and the use of currently available prescreening methods for large-scale genetic epidemiological research until more advanced sequencing methods currently under development will become available.