The challenges for molecular nutrition research 1: linking genotype to healthy nutrition

Nutrition science finds itself at a major crossroad. On the one hand we can continue the current path, which has resulted in some substantial advances, but also many conflicting messages which impair the trust of the general population, especially those who are motivated to improve their health through diet. The other road is uncharted and is being built over the many exciting new developments in life sciences. This new era of nutrition recognizes the complex relation between the health of the individual, its genome, and the life-long dietary exposure, and has lead to the realisation that nutrition is essentially a gene - environment interaction science. This review on the relation between genotype, diet and health is the first of a series dealing with the major challenges in molecular nutrition, analyzing the foundations of nutrition research. With the unravelling of the human genome and the linking of its variability to a multitude of phenotypes from " healthy'' to an enormously complex range of predispositions, the dietary modulation of these propensities has become an area of active research. Classical genetic approaches applied so far in medical genetics have steered away from incorporating dietary effects in their models and paradoxically, most genetic studies analyzing diet-associated phenotypes and diseases simply ignore diet. Yet, a modest but increasing number of studies are accounting for diet as a modulator of genetic associations. These range from observational cohorts to intervention studies with prospectively selected genotypes. New statistical and bioinformatics approaches are becoming available to aid in design and evaluation of these studies. This review discusses the various approaches used and provides concrete recommendations for future research.

Biomarkers of the intake of dietary polyphenols: strengths, limitations and application in nutrition research

In order to establish firm evidence for the health effects of dietary polyphenol consumption, it is essential to have quantitative information regarding their dietary intake. The usefulness of the current methods, which rely mainly on the assessment of polyphenol intake using food records and food composition tables, is limited as they fail to assess total intake accurately. This review highlights the problems associated with such methods with regard to polyphenol-intake predictions. We suggest that the development of biological biomarkers, measured in both blood and urine, are essential for making accurate estimates of polyphenol intake. However, the relationship between dietary intakes and nutritional biomarkers are often highly complex. This review identifies the criteria that must be considered in the development of such biomarkers. In addition, we provide an assessment of the limited number of potential biomarkers of polyphenol intake currently available.

Nutrition Society Silver Medal Lecture Nutrigenetics and personalised nutrition: how far have we progressed and are we likely to get there?

Nutrigenetics and personalised nutrition are components of the concept that in the future genotyping will be used as a means of defining dietary recommendations to suit the individual. Over the last two decades there has been an explosion of research in this area, with often conflicting findings reported in the literature. Reviews of the literature in the area of apoE genotype and cardiovascular health, apoA5 genotype and postprandial lipaemia and perilipin and adiposity are used to demonstrate the complexities of genotype-phenotype associations and the aetiology of apparent between-study inconsistencies in the significance and size of effects. Furthermore, genetic research currently often takes a very reductionist approach, examining the interactions between individual genotypes and individual disease biomarkers and how they are modified by isolated dietary components or foods. Each individual possesses potentially hundreds of 'at-risk' gene variants and consumes a highly-complex diet. In order for nutrigenetics to become a useful public health tool, there is a great need to use mathematical and bioinformatic tools to develop strategies to examine the combined impact of multiple gene variants on a range of health outcomes and establish how these associations can be modified using combined dietary strategies.

Probiotics and prebiotics in infant nutrition

The human colonic microflora has a central role in health and disease, being unique ill its complexity and range of functions. As such, dietary modulation is important for improved gut health, especially during the highly-sensitive stage of infancy. Diet call affect the composition of the gut microflora through the availability of different substrates for bacterial fermentation. Differences in gut microflora composition and incidence of infection exist between breast-fed and formula-fed infants, with the former thought to have improved protection. Historically, this improvement has been believed to be a result of the higher presence of reportedly-beneficial genera such as the bifidobacteria. As such, functional food ingredients such as prebiotics and probiotics could effect a beneficial modification in the composition and activities of gut microflora of infants by increasing positive flora components. The prebiotic approach aims to increase resident bacteria that are considered to be beneficial for human health, e.g. bifidobacteria and lactobacilli, while probiotics advocates the use of the live micro-organisms themselves in the diet. Both approaches have found their way into infant formula feeds and aim to more closely simulate the gut microbiota composition seen during breast-feeding.

Personalized nutrition for the prevention of cardiovascular disease: a future perspective

Cardiovascular disease (CVD) is responsible for significant morbidity and mortality in the Western and developing world. This multifactorial disease is influenced by many environmental and genetic factors. At present, public health advice involves prescribed population-based recommendations, which have been largely unsuccessful in reducing CVD risk. This is, in part, due to individual variability in response to dietary manipulations, that arises from nutrient-gene interactions (defined by the term 'nutrigenetics'). The shift towards personalized nutritional advice is a very attractive proposition, where, in principle, an individual can be given dietary advice specifically tailored to their genotype. However, the evidence-base for the impact of interactions between nutrients and fixed genetic variants on biomarkers of CVD risk is still very limited. This paper reviews the evidence for interactions between dietary fat and two common polymorphisms in the apolipoprotein E and peroxisome proliferator-activated receptor-gamma genes. Although an increased understanding of how these and other genes influence response to nutrients should facilitate the progression of personalized nutrition, the ethical issues surrounding its routine use need careful consideration.

Symposium on 'nutrition interventions in high-risk groups' - CVD risk in South Asians: the importance of defining adiposity and influence of dietary polyunsaturated fat

The prevalence of the metabolic syndrome (MetS), CVD and type 2 diabetes (T2D) is known to be higher in populations from the Indian subcontinent compared with the general UK population. While identification of this increased risk is crucial to allow for effective treatment, there is controversy over the applicability of diagnostic criteria, and particularly measures of adiposity in ethnic minorities. Diagnostic cut-offs for BMI and waist circumference have been largely derived from predominantly white Caucasian populations and, therefore, have been inappropriate and not transferable to Asian groups. Many Asian populations, particularly South Asians, have a higher total and central adiposity for a similar body weight compared with matched Caucasians and greater CVD risk associated with a lower BMI. Although the causes of CVD and T2D are multi-factorial, diet is thought to make a substantial contribution to the development of these diseases. Low dietary intakes and tissue levels of long-chain (LC) n-3 PUFA in South Asian populations have been linked to high-risk abnormalities in the MetS. Conversely, increasing the dietary intake of LC n-3 PUFA in South Asians has proved an effective strategy for correcting such abnormalities as dyslipidaemia in the MetS. Appropriate diagnostic criteria that include a modified definition of adiposity must be in place to facilitate the early detection and thus targeted treatment of increased risk in ethnic minorities.

Personalised nutrition: status and perspectives

Personalised, genotype-based nutrition is a concept that links genotyping with specific nutritional advice in order to improve the prevention of nutrition-associated, chronic diseases. This review describes the current scientific basis of the concept and discusses its problems. There is convincing evidence that variant genes may indeed determine the biological response to nutrients. The effects of single-gene variants on risk or risk factor levels of a complex disease are, however, usually small and sometimes inconsistent. Thus, information on the effects of combinations of relevant gene variants appears to be required in order to improve the predictive precision of the genetic information. Furthermore, very few associations between genotype and response have been tested for causality in human intervention studies, and little is known about potential adverse effects of a genotype-derived intervention. These issues need to be addressed before genotyping can become an acceptable method to guide nutritional recommendations.

Understanding prebiotics in infant and childhood nutrition

Prebiotics and probiotics are ingredients in the diet that strengthen beneficial microbes in the gut, especially bifidobacteria. This article discusses their effects on health and their use in infant formula and foods for children and adults. They may also have benefits for the elderly population, since bifidobacteria are known to decrease with old age.

Effects of plant sulfur nutrition on acrylamide and aroma compounds in cooked wheat

Wheat flour from plants deficient in sulfur has been shown to contain substantially higher levels of free amino acids, particularly asparagine and glutamine, than flour from wheat grown where sulfur nutrition was sufficient. Elevated levels of asparagine resulted in acrylamide levels up to 6 times higher in sulfur-deprived wheat flour, compared with sulfur-sufficient wheat flour, for three varieties of winter wheat. The volatile compounds from flour, heated at 180 degrees C for 20 min, have been compared for these three varieties of wheat grown with and without sulfur fertilizer. Approximately 50 compounds were quantified in the headspace extracts of the heated flour; over 30 compounds were affected by sulfur fertilization, and 15 compounds were affected by variety. Unsaturated aldehydes formed from aldol condensations, Strecker. aldehydes, alkylpyrazines, and low molecular weight alkylfurans were found at higher concentrations in the sulfur-deficient flour, whereas low molecular weight pyrroles and thiophenes and sugar breakdown products were found at higher concentrations in the sulfur-sufficient flour. The reasons for these differences and the relationship between acrylamide formation and aroma volatile formation are discussed.

Global climate change and tree nutrition: effects of elevated CO2 and temperature

Although tree nutrition has not been the primary focus of large climate change experiments on trees, we are beginning to understand its links to elevated atmospheric CO2 and temperature changes. This review focuses on the major nutrients, namely N and P, and deals with the effects of climate change on the processes that alter their cycling and availability. Current knowledge regarding biotic and abiotic agents of weathering, mobilization and immobilization of these elements will be discussed. To date, controlled environment studies have identified possible effects of climate change on tree nutrition. Only some of these findings, however, were verified in ecosystem scale experiments. Moreover, to be able to predict future effects of climate change on tree nutrition at this scale, we need to progress from studying effects of single factors to analysing interactions between factors such as elevated CO2, temperature or water availability.

Effects of sulphur nutrition during potato cultivation on the formation of acrylamide and aroma compounds during cooking

Lack of sulphur nutrition during potato cultivation has been shown to have profound effects on tuber composition, affecting in particular the concentrations of free asparagine, other amino acids and sugars. This is important because free asparagine and sugars react at high temperatures to form acrylamide, a suspect carcinogen. Free amino acids and sugars also form a variety of other compounds associated with colour and flavour. In this study the volatile aroma compounds formed in potato flour heated at 180 °C for 20 min were compared for three varieties of potato grown, with and without sulphur fertiliser. Approximately 50 compounds were quantified in the headspace extracts of the heated flour, of which over 40 were affected by sulphur fertilisation and/or variety. Many of the 41 compounds found at higher concentrations in the sulphur-deficient flour were Strecker aldehydes and compounds formed from their condensation, whereas only one compound, benzaldehyde, behaved in the same way as did acrylamide and was found at higher concentrations in the sulphur-sufficient flour. The reasons for these effects are discussed.

Glomus intraradices and Gigaspora margarita arbuscular mycorrhizal associations differentially affect nitrogen and potassium nutrition of Plantago lanceolata in a low fertility dune soil

Two controlled microcosm experiments aimed at a critical re-assessment of the contributions of divergent arbuscular mycorrhizal (AM) fungi to plant mineral nutrition were established that specifically targeted Plantago lanceolata–Glomus intraradices (B.B/E) and –Gigaspora margarita (BEG 34) symbioses developed in a native, nutrient limited, coastal dune soil. Plant tissue nitrogen (N), phosphorus (P) and potassium (K) status as well as plant growth parameters and levels of mycorrhizal colonization were assessed at harvest. In addition to the general well-established mycorrhizal facilitation of P uptake, the study was able to demonstrate a G. intraradices-specific contribution to improved plant nitrogen and potassium nutrition. In the two respective experiments, G. intraradices-inoculated plants had 27.8% and 40.8% more total N and 55.8% and 23.3% more total K when compared to Gi. margarita inoculated counterparts. Dissimilar overall contribution of the two isolates to plant nutrition was identified in AM-genus specific differences in plant tissue N:P:K ratios. G. intraradices inoculated and non-mycorrhizal plants generally exhibited N:P:K ratios indicative of P limitation whereas for Gi.margarita mycorrhizal plants, corresponding ratios strongly implied either N or K limitation. The study provides further evidence highlighting AM functional biodiversity in respect to plant nutrient limitation experienced by mycorrhizal P. lanceolata in an ecologically relevant soil system.