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.     

营养基因组学的研究进展

伴随着基因组学、生物信息学等的迅猛发展及其在生命科学领域的应用,营养基因组学应运而生,并迅速成为营养学研究的新前沿。营养基因组学主要研究营养素和植物化学物质对人体基因的转录、翻译表达以及代谢机制,其可能的应用范围包括营养素作用的分子机制、营养素的人体需要量、个体食谱的制定以及食品安全等。本文重点介绍营养基因组学的研究内容与现状,并对今后的研究趋势作了展望。     

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.     

NutriTRAILomics in prostate cancer: time to have two strings to one’s bow

The astonishing development of broad genomics and proteomics tools have catalyzed a new era in both therapeutic interventions and nutrition in prostate cancer. The terms pharmacogenomics and nutrigenomics have been derived out of their genetic forbears as large-scale genomics technologies have been established in the last decade. It is unquestionable that rationale of both disciplines is to individualize or personalize medicine and food and nutrition, and eventually health, by tailoring the drug or the food to the individual genotype. The purpose of this review is to significantly inspect results from current research concerning the mechanisms of action of phytonutrients and potential effects on prostate cancer. Substantial emerging data supports the synergistic adiministration of nutraceuticals with TRAIL in prostate cancer progression to circumvent TRAIL refractoriness. Nonetheless, developing novel scientific methods for discovery, validation, characterization and standardization of these multicomponent phyto-therapeutics is vital to their recognition into mainstream medicine. The key to interpret a personalized response is a greater comprehension of nutrigenomics, proteomics and metabolomics.     

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.     

The human gutome: nutrigenomics of the host-microbiome interactions

Demonstrating the importance of the gut microbiota in human health and well-being represents a major transformational task in both medical and nutritional research. Owing to the high-throughput -omics methodologies, the complexity, evolution with age, and individual nature of the gut microflora have been more thoroughly investigated. The balance between this complex community of gut bacteria, food nutrients, and intestinal genomic and physiological milieu is increasingly recognized as a major contributor to human health and disease. This article discusses the "gutome," that is, nutritional systems biology of gut microbiome and host-microbiome interactions. We examine the novel ways in which the study of the human gutome, and nutrigenomics more generally, can have translational and transformational impacts in 21st century practice of biomedicine. We describe the clinical context in which experimental methodologies, as well as data-driven and process-driven approaches are being utilized in nutrigenomics and microbiome research. We underscore the pivotal importance of the gutome as a common platform for sharing data in the emerging field of the integrated metagenomics of gut pathophysiology. This vision needs to be articulated in a manner that recognizes both the omics biotechnology nuances and the ways in which nutrigenomics science can effectively inform population health and public policy, and vice versa.     

PIWI-interacting RNA (piRNA) signatures in human cardiac progenitor cells

Cardiac progenitors, such as cardiospheres and cardiosphere-derived cells, represent an attractive cell source for cardiac regeneration. The PIWI-interacting RNAs, piRNAs, are an intriguing class of small non-coding RNAs, implicated in the regulation of epigenetic state, maintenance of genomic integrity and stem cell functions. Although non-coding RNAs are an exploiting field in cardiovascular research, the piRNA signatures of cardiac progenitors has not been evaluated yet.We profiled, through microarrays, 15,311 piRNAs expressed in cardiospheres, cardiosphere-derived cells and cardiac fibroblasts. Results showed a set of differentially expressed piRNAs (fold change ≥2, p < 0.01): 641 piRNAs were upregulated and 1,301 downregulated in the cardiospheres compared to cardiosphere-derived cells, while 255 and 708 piRNAs resulted up- and down-regulated, respectively, if compared to cardiac fibroblasts. We also identified 181 piRNAs that are overexpressed and 129 are downregulated in cardiosphere-derived cells respect to cardiac fibroblasts.Bioinformatics analysis showed that the deregulated piRNAs were mainly distributed on few chromosomes, suggesting that piRNAs are organized in discrete genomic clusters.Furthermore, the bioinformatics search showed that the most upregulated piRNAs target transposons, especially belonged to LINE-1 class, as validated by qRT-PCR. This reduction is also associated to an activation of AKT signaling, which is beneficial for cardiac regeneration.The present study is the first to show a highly consistent piRNA expression pattern for human cardiac progenitors, likely responsible of their different regenerative power. Moreover, this piRNome analysis may provide new methods for characterize cardiac progenitors and may shed new light on the understanding the complex molecular mechanisms of cardiac regeneration.     

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.     

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.     

Nutrigenomics and nutrigenetics

PURPOSE OF REVIEW: Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutritional genomics covers nutrigenomics, which explores the effects of nutrients on the genome, proteome and metabolome, and nutrigenetics, the major goal of which is to elucidate the effect of genetic variation on the interaction between diet and disease. Nutrigenetics has been used for decades in certain rare monogenic diseases such as phenylketonuria, and it has the potential to provide a basis for personalized dietary recommendations based on the individual's genetic makeup in order to prevent common multifactorial disorders decades before their clinical manifestation. RECENT FINDINGS: Preliminary results regarding gene-diet interactions in cardiovascular diseases are for the most part inconclusive because of the limitations of current experimental designs. Success in this area will require the integration of various disciplines, and will require investigators to work on large population studies that are designed to investigate gene-environment interactions. SUMMARY: Based on the current knowledge, we anticipate that in the future we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes, with nutrition being the cornerstone of this endeavor.     

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.     

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。     

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.     

Use of miRNAs in biofluids as biomarkers in dietary and lifestyle intervention studies

The selection of biomarkers in nutrigenomics needs to reflect subtle changes in homoeostasis representing the relation between nutrition and health, or nutrition and disease. It is believed that noncoding RNAs, such as circulating microRNAs (miRNAs), may represent such a new class of integrative biomarkers. Until now, the most relevant body fluids for miRNA quantification in response to nutrition have not been clearly defined, but recent studies listed in this review indicate that miRNAs from plasma or serum, PBMC and faeces might be relevant biomarkers to quantify the physiological impacts of dietary or lifestyle intervention studies. In addition, a number of recent studies also indicate that miRNAs could permit to monitor the impact of diet on gut microbiota. We also discuss the main preanalytical considerations that are important to take into account before miRNA screening which can affect the reproducibility of the data.     

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.     

Enfermedad cardiovascular tras infección por SARS-CoV-2 en pacientes ancianos. Resultados del seguimiento anual de una cohorte de supervivientes

IntroductionAlthough the effects of SARS-CoV-2 infection on the cardiovascular system is well known in the acute phase, the cardiovascular impact of the elderly population surviving COVID-19 respiratory infection after 1 year of follow-up has not been sufficiently studied.MethodsObservational registry of 240 elderly patients (75 years or older), consecutively admitted for COVID-19 respiratory infection and survivors of the same, between March 1 and April 30, 2020, at the Hospital General Universitario de Ciudad Real. The incidence of major cardiovascular events [MACE] (cardiovascular death [CD], acute coronary syndrome [ACS], cerebrovascular disease [CVD], venous thromboembolic disease [VTE] and heart failure [HF]) was prospectively analysed.ResultsThe mean age was 83.75 ± 5.75 years. After a mean follow-up of 352.2 ± 70.4 days, 13.8% of patients died and 9.6% had MACE, the most frequent being heart failure, with no differences in severity or overall course of acute illness. In the multivariate Cox regression model, the risk of developing MACE was higher in patients with chronic obstructive pulmonary disease and (HR 4.29; 95%CI 1.62-11.39; P = .003) and loop diuretic (HR 2.99; 95%CI 1.27-7.07; P = .01).ConclusionsIn elderly COVID-19 survivors, the incidence of MACE after one year of follow-up is high, the main manifestation being heart failure.