Neurobiology of eating behavior, nutrition, and health.

Eating behavior and food-related decision making are among the most complex of the motivated behaviors, and understanding the neurobiology of eating behavior, and its developmental dynamics, is critical to advancing the nutritional sciences and public health. Recent advances from both human and animal studies are revealing that individual capacity to make health-promoting food decisions varies based on biological and physiological variation in the signaling pathways that regulate the homeostatic, hedonic, and executive functions; past developmental exposures and current life-stage; the food environment; and complications of chronic disease that reinforce the obese state. Eating rate drives increased calorie intake and represents an important opportunity to lower rates of food consumption and energy intake through product reformulation. Understanding human eating behaviors and nutrition in the context of neuroscience can strengthen the evidence base from which dietary guidelines are derived and can inform policies, practices, and educational programs in a way that increases the likelihood they are adopted and effective for reducing rates of obesity and other diet-related chronic disease.

Optimization of Electrospray Ionization Source Parameters for Lipidomics To Reduce Misannotation of In-Source Fragments as Precursor Ions.

Lipidomics requires the accurate annotation of lipids in complex samples to enable determination of their biological relevance. We demonstrate that unintentional in-source fragmentation (ISF, common in lipidomics) generates ions that have identical masses to other lipids. Lysophosphatidylcholines (LPC), for example, generate in-source fragments with the same mass as free fatty acids and lysophosphatidylethanolamines (LPE). The misannotation of in-source fragments as true lipids is particularly insidious in complex matrixes since most masses are initially unannotated and comprehensive lipid standards are unavailable. Indeed, we show such LPE/LPC misannotations are incorporated in the data submitted to the National Institute of Standards and Technology (NIST) interlaboratory comparison exercise. Computer simulations exhaustively identified potential misannotations. The selection of in-source fragments of highly abundant lipids as features, instead of the correct recognition of trace lipids, can potentially lead to (i) missing the biologically relevant lipids (i.e., a false negative) and/or (ii) incorrect assignation of a phenotype to an incorrect lipid (i.e., false positive). When ISF is not eliminated in the negative ion mode, ∼40% of the 100 most abundant masses corresponding to unique phospholipids measured in plasma were artifacts from ISF. We show that chromatographic separation and ion intensity considerations assist in distinguishing precursor ions from in-source fragments, suggesting ISF may be especially problematic when complex samples are analyzed via shotgun lipidomics. We also conduct a systematic evaluation of electrospray ionization (ESI) source parameters on an Exactive equipped with a heated electrospray ionization (HESI-II) source with the objective of obtaining uniformly appropriate source conditions for a wide range of lipids, while, at the same time, reducing in-source fragmentation.

Diet, Microbiome, and Epigenetics in the Era of Precision Medicine.

Precision medicine is a revolutionary approach to disease prevention and treatment that takes into account individual differences in lifestyle, environment, and biology. The US National Institutes of Health has recently launched The All of Us Research Program (2016) to extend precision medicine to all diseases by building a national research cohort of one million or more US participants. This review is limited to how the human microbiome factors into precision medicine from the applied aspect of preventing and managing cancer. The Precision Medicine Initiative was established in an effort to address particular characteristics of each person with the aim to increase the effectiveness of medical interventions in terms of prevention and treatment of multiple diseases including cancer. Many factors contribute to the response to an intervention. The microbiome and microbially produced metabolites are capable of epigenetic modulation of gene activity, and can influence the response through these mechanisms. The fact that diet has an impact on microbiome implies that it will also affect the epigenetic mechanisms involving microbiota. In this chapter, we review some major epigenetic mechanisms, notably DNA methylation, chromatin remodeling and histone modification, and noncoding RNA, implicated in cancer prevention and treatment. Several examples of how microbially produced metabolites from food influence cancer risk and treatment response through epigenetic mechanisms will be discussed. Some challenges include the limited understanding of how diet shapes the microbiome and how to best evaluate those changes since both, diet and the microbiota, exhibit daily and seasonal variations. Ongoing research seeks to understand the relationship between the human microbiome and multiple diseases including cancer.

Developmental Process and Early Phases of Implementation for the US Interagency Committee on Human Nutrition Research National Nutrition Research Roadmap 2016-2021.

The Interagency Committee on Human Nutrition Research (ICHNR) is charged with improving the planning, coordination, and communication among federal agencies engaged in nutrition research and with facilitating the development and updating of plans for federal research programs to meet current and future domestic and international needs for nutrition. The ICHNR is co-chaired by the USDA Under Secretary for Research, Education, and Economics and Chief Scientist and the US Department of Health and Human Services Assistant Secretary for Health and is made up of >10 departments and agencies. Once the ICHNR was reassembled after a 10-y hiatus, the ICHNR recognized a need for a written roadmap to identify critical human nutrition research gaps and opportunities. This commentary provides an overview of the process the ICHNR undertook to develop a first-of-its-kind National Nutrition Research Roadmap, which was publicly released on 4 March 2016. The primary audience for the Roadmap is federal science agency leaders, along with relevant program and policy staff who rely on federally supported human nutrition research, in addition to the broader scientific community. The Roadmap is framed around the following 3 questions: 1) How can we better understand and define eating patterns to improve and sustain health? 2) What can be done to help people choose healthy eating patterns? 3) How can we develop and engage innovative methods and systems to accelerate discoveries in human nutrition? Within these 3 questions, 11 topical areas were identified on the basis of the following criteria: population impact, feasibility given current technological capacities, and emerging scientific opportunities. This commentary highlights initial federal and some professional research society efforts to address the Roadmap's research and resource priorities. We conclude by noting examples of early collaborations and partnerships to move human nutrition research forward in the 21st century.

Omics for Understanding the Gut-Liver-Microbiome Axis and Precision Medicine.

Human metabolic disease opens a new view to understanding the contribution of the intestinal microbiome to drug metabolism and drug-induced toxicity in gut-liver function. The gut microbiome, a key determinant of intestinal inflammation, also plays a direct role in chronic inflammation and liver disease. Gut bacterial communities directly metabolize certain drugs, reducing their bioavailability and influencing individual variation in drug response. In addition, some microbiome-produced compounds may affect drug pharmacokinetics and pharmacodynamics via altered expression of metabolizing enzymes and drug transporters or genes coding for drug target proteins, drug response phenotypes, and disease states. Molecular-based high-throughput technologies are providing novel insight about host-gut microbiome interactions, homeostasis, and xenobiotic effects associated with wide variation in efficacy or toxicity in humans. It is envisioned that future approaches to treating and preventing liver disease will benefit from in-depth studies of the liver-microbiome axis. Thus, the microbiome shares a fundamental role in human physiology with various organ systems, and its importance must be considered in the rapid evolution of precision medicine. A new emerging perspective of understanding the effect of the gut microbiome on human response to drugs would be indispensable for developing efficacious, safe, and cost-effective precision therapies.

Progress and challenges in developing metabolic footprints from diet in human gut microbial cometabolism.

Homo sapiens harbor trillions of microbes, whose microbial metagenome (collective genome of a microbial community) using omic validation interrogation tools is estimated to be at least 100-fold that of human cells, which comprise 23,000 genes. This article highlights some of the current progress and open questions in nutrition-related areas of microbiome research. It also underscores the metabolic capabilities of microbial fermentation on nutritional substrates that require further mechanistic understanding and systems biology approaches of studying functional interactions between diet composition, gut microbiota, and host metabolism. Questions surrounding bacterial fermentation and degradation of dietary constituents (particularly by Firmicutes and Bacteroidetes) and deciphering how microbial encoding of enzymes and derived metabolites affect recovery of dietary energy by the host are more complex than previously thought. Moreover, it is essential to understand to what extent the intestinal microbiota is subject to dietary control and to integrate these data with functional metabolic signatures and biomarkers. Many lines of research have demonstrated the significant role of the gut microbiota in human physiology and disease. Probiotic and prebiotic products are proliferating in the market in response to consumer demand, and the science and technology around these products are progressing rapidly. With high-throughput molecular technologies driving the science, studying the bidirectional interactions of host-microbial cometabolism, epithelial cell maturation, shaping of innate immune development, normal vs. dysfunctional nutrient absorption and processing, and the complex signaling pathways involved is now possible. Substantiating the safety and mechanisms of action of probiotic/prebiotic formulations is critical. Beneficial modulation of the human microbiota by using these nutritional and biotherapeutic strategies holds considerable promise as next-generation drugs, vaccinomics, and metabolic agents and in novel food discovery.

Challenges and new opportunities for clinical nutrition interventions in the aged.

Nutritional status plays a critical role in the prevention and management of many chronic health conditions that are common in the elderly and are likely to become more prevalent as the population ages. This paper highlights several aspects of nutrition that require additional basic science and clinical application research to improve the health and well-being of older adults. Topics addressed are selected demographic and health indices, the uncertain benefits of energy restriction in aged humans compared with other species, the impact of food insecurity on health, the relationship between dietary protein and sarcopenia, the prevention and management of obesity while maintaining muscle mass and functional status, and controversy regarding high intakes of folic acid. Research needs regarding the safety, efficacy, and application of clinical interventions related to these topics also are discussed.

Guidance from an NIH workshop on designing, implementing, and reporting clinical studies of soy interventions.

The NIH sponsored a scientific workshop, "Soy Protein/Isoflavone Research: Challenges in Designing and Evaluating Intervention Studies," July 28-29, 2009. The workshop goal was to provide guidance for the next generation of soy protein/isoflavone human research. Session topics included population exposure to soy; the variability of the human response to soy; product composition; methods, tools, and resources available to estimate exposure and protocol adherence; and analytical methods to assess soy in foods and supplements and analytes in biologic fluids and other tissues. The intent of the workshop was to address the quality of soy studies, not the efficacy or safety of soy. Prior NIH workshops and an evidence-based review questioned the quality of data from human soy studies. If clinical studies are pursued, investigators need to ensure that the experimental designs are optimal and the studies properly executed. The workshop participants identified methodological issues that may confound study results and interpretation. Scientifically sound and useful options for dealing with these issues were discussed. The resulting guidance is presented in this document with a brief rationale. The guidance is specific to soy clinical research and does not address nonsoy-related factors that should also be considered in designing and reporting clinical studies. This guidance may be used by investigators, journal editors, study sponsors, and protocol reviewers for a variety of purposes, including designing and implementing trials, reporting results, and interpreting published epidemiological and clinical studies.

Nanotechnology research: applications in nutritional sciences.

The tantalizing potential of nanotechnology is to fabricate and combine nanoscale approaches and building blocks to make useful tools and, ultimately, interventions for medical science, including nutritional science, at the scale of approximately 1-100 nm. In the past few years, tools and techniques that facilitate studies and interventions in the nanoscale range have become widely available and have drawn widespread attention. Recently, investigators in the food and nutrition sciences have been applying the tools of nanotechnology in their research. The Experimental Biology 2009 symposium entitled "Nanotechnology Research: Applications in Nutritional Sciences" was organized to highlight emerging applications of nanotechnology to the food and nutrition sciences, as well as to suggest ways for further integration of these emerging technologies into nutrition research. Speakers focused on topics that included the problems and possibilities of introducing nanoparticles in clinical or nutrition settings, nanotechnology applications for increasing bioavailability of bioactive food components in new food products, nanotechnology opportunities in food science, as well as emerging safety and regulatory issues in this area, and the basic research applications such as the use of quantum dots to visualize cellular processes and protein-protein interactions. The session highlighted several emerging areas of potential utility in nutrition research. Nutrition scientists are encouraged to leverage ongoing efforts in nanomedicine through collaborations. These efforts could facilitate exploration of previously inaccessible cellular compartments and intracellular pathways and thus uncover strategies for new prevention and therapeutic modalities.

The NIH Human Microbiome Project.

The Human Microbiome Project (HMP), funded as an initiative of the NIH Roadmap for Biomedical Research (http://nihroadmap.nih.gov), is a multi-component community resource. The goals of the HMP are: (1) to take advantage of new, high-throughput technologies to characterize the human microbiome more fully by studying samples from multiple body sites from each of at least 250 "normal" volunteers; (2) to determine whether there are associations between changes in the microbiome and health/disease by studying several different medical conditions; and (3) to provide both a standardized data resource and new technological approaches to enable such studies to be undertaken broadly in the scientific community. The ethical, legal, and social implications of such research are being systematically studied as well. The ultimate objective of the HMP is to demonstrate that there are opportunities to improve human health through monitoring or manipulation of the human microbiome. The history and implementation of this new program are described here.

Dietary reference intakes for vitamin D: justification for a review of the 1997 values.

Recent Institute of Medicine (IOM) reviews of the process for deriving Dietary Reference Intakes (DRIs) suggest that determining the need for a new nutrient review should be evaluated against criteria set a priori. After selecting the criterion of significant new and relevant research, a working group of US and Canadian government scientists used results from a systematic review and 2 conferences on vitamin D and health to evaluate whether significant new and relevant scientific evidence had become available since the 1997 IOM publication of the DRIs for vitamin D. This working group concluded that there appears to be new research meeting the criteria for 4 key DRI questions. The new research is of larger quantity and quality for the elderly than for other groups, but overall 1) adds to the bone-related and status evidence available to the 1997 DRI Committee for several of the life-stage groups, 2) identifies new outcomes with respect to risk of falls and performance measures in the elderly and potential adverse effects, and 3) provides additional information on dose-response relations between intakes and circulating 25-hydroxyvitamin D concentrations and between 25-hydroxyvitamin D concentrations and several health outcomes (ie, bone-related outcomes for all ages and risk of falls and performance measures in older adults). Members of the working group concluded that significant new and relevant research was available for reviewing the existing DRIs for vitamin D while leaving the decision of whether the new research will result in changes to the current DRIs to a future IOM-convened DRI committee.

The change in weight perception of weight status among the overweight: comparison of NHANES III (1988-1994) and 1999-2004 NHANES.

OBJECTIVES: This study seeks to determine whether perception of weight status among the overweight has changed with the increasing overweight/obesity prevalence. METHODS: The perception of weight status was compared between overweight participants (BMI between 25.0-29.9 kg/m2) from NHANES III (1988-1994) and overweight participants from NHANES 1999-2004. Perception of weight status was assessed by asking participants to classify their weight as about the right weight, underweight or overweight. Comparisons were made across age groups, genders, race/ethnicities and various income levels. RESULTS: Fewer overweight people during the NHANES 1999-2004 survey perceived themselves as overweight when compared to overweight people during the NHANES III survey. The change in distortion between the survey periods was greatest among persons with lower income, males and African-Americans. CONCLUSION: The increase in overweight/obesity between the survey years (NHANES III and NHANES 1999-2004 has been accompanied with fewer overweight people perceiving themselves as overweight.

Green tea extract suppresses the age-related increase in collagen crosslinking and fluorescent products in C57BL/6 mice.

Collagen crosslinking during aging in part results from Maillard reaction endproducts of glucose and oxoaldehydes. Because of the tight link between oxidative and carbonyl stress, we hypothesized that natural antioxidants and "nutriceuticals" could block collagen aging in C57BL/6 mice. Six groups of young and adult mice received vitamin C, vitamin E, vitamin C&E, blueberry, green tea extract (GTE), or no treatment for a period of 14 weeks. Body weights and collagen glycation were unaltered by the treatment. However, GTE or vitamin C&E combined blocked tendon crosslinking at 10 months of age (p < 0.05, adult group). GTE also blocked fluorescent products at 385 and 440 nm (p = 0.052 and < 0.05, respectively) and tended to decrease skin pentosidine levels. These results suggest that green tea is able to delay collagen aging by an antioxidant mechanism that is in part duplicated by the combination of vitamin C and E.

Summary of the 2000 Surgeon General's listening session: toward a national action plan on overweight and obesity.

OBJECTIVE: To provide insight into discussions at the Surgeon General's Listening Session, "Toward a National Action Plan on Overweight and Obesity," and to complement The Surgeon General's Call to Action to Prevent and Decrease Overweight and Obesity. RESEARCH METHODS AND PROCEDURES: On December 7 and 8, 2000, representatives from federal, state, academic, and private sectors attended the Surgeon General's Listening Session and were given an opportunity to recommend what to include in a national plan to address overweight and obesity. The public was invited to comment during a corresponding public comment period. The Surgeon General's Listening Session was also broadcast on the Internet, allowing others to view the deliberations live or access the archived files. Significant discussion points from the Listening Session have been reviewed by representatives of the federal agencies and are the basis of this complementary document. RESULTS: Examples of issues, strategies, and barriers to change are discussed within five thematic areas: schools, health care, family and community, worksite, and media. Suggested cooperative or collaborative actions for preventing and decreasing overweight and obesity are described. An annotated list of some programmatic partnerships is included. DISCUSSION: The Surgeon General's Listening Session provided an opportunity for representatives from family and community groups, schools, the media, the health-care environment, and worksites to become partners and to unite around the common goal of preventing and decreasing overweight and obesity. The combination of approaches from these perspectives offers a rich resource of opportunity to combat the public health epidemic of overweight and obesity.