Nutritional genomics is a new and promising science area which can broadly be defined as the application of high throughput genomics (transcriptomics, proteomics, metabolomics/metabonomics) and functional genomic technologies to the study of nutritional sciences and food technology. First utilised in the food industry by plant biotechnologists to manipulate plant biosynthetic pathways, the use of genomic technologies has now spread within the agriculture sector, unleashing a host of new applications (e.g. approaches for producing novel, non-transgenic plant varietals; identification of genetic markers to guide plant and animal breeding programmes; exploration of diet–gene interactions for enhancing product quality and plant/animal health). Beyond agriculture, genomic technologies are also contributing to the improvement of food processing, food safety and quality assurance as well as the development of functional food products and the evolution of new health management concepts such as ‘personalised nutrition’, an emerging paradigm in which the diet of an individual is customised, based on their own genomic information, to optimise health and prevent disease. In this review the relevance of nutritional genomics to the food industry will be considered and examples given on how this science area is starting to be leveraged for economic benefits and to improve human nutrition and health.

There is considerable evidence for the induction of different phenotypes by variations in the early life environment, including nutrition, which in man is associated with a graded risk of metabolic disease; fetal programming. It is likely that the induction of persistent changes to tissue structure and function by differences in the early life environment involves life-long alterations to the regulation of gene transcription. This view is supported by both studies of human subjects and animal models. The mechanism which underlies such changes to gene expression is now beginning to be understood. In the present review we discuss the role of changes in the epigenetic regulation of transcription, specifically DNA methylation and covalent modification of histones, in the induction of an altered phenotype by nutritional constraint in early life. The demonstration of altered epigenetic regulation of genes in phenotype induction suggests the possibility of interventions to modify long-term disease risk associated with unbalanced nutrition in early life.

Several food items of plant origin, and in particular red wine, have been reported to protect from cardiovascular disease (CVD) development, thanks to their polyphenol components. Polyphenols undergo complex metabolic transformation during digestion and intestinal absorption. Here we report a novel model to study the effects of complex food matrices, applied to red wine, on gene expression in cultured primary human endothelial cells that takes into account the polyphenol metabolic transformation. Red wine was administered to human volunteers acting as ‘bio-reactors’. Serum (RWS) obtained after 40 min was utilized to enrich endothelial cell culture media. The expression of specific genes involved in cell adhesion (vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM) and monocytes chemoattractant protein (MCP-1)) and fibrinolysis (tissue-plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2)) was considered as a molecular marker of cell function and related to the effects of RWS. The gene expression profile determined by RWS incubation was significantly different from that observed after the addition of red wine. Data obtained by this approach indicate the importance of taking into account the complex metabolic transformation of polyphenols that occurs during absorption when studying their effect on human health.

A theoretical equation was developed by Forbes that quantifies the fat-free proportion of a weight change as a function of the initial body fat. However, Forbes's equation was strictly valid only for infinitesimal weight changes. Here, I extended Forbes's equation to account for the magnitude and direction of macroscopic body weight changes. The new equation was also re-expressed in terms of an alternative representation of body composition change defined by an energy partitioning parameter called the P-ratio. The predictions of the resulting equations compared favourably with data from human underfeeding and overfeeding experiments and accounted for previously unexplained trends in the data. The magnitude of the body weight change had a relatively weak effect on the predicted body composition changes and the results were very similar to Forbes's original equation for modest weight changes. However, for large weight changes, such as the massive weight losses found in patients following bariatric surgery, Forbes's original equation consistently underestimated the fat-free mass loss, as expected. The new equation that accounts for the magnitude of the weight loss provides better predictions of body composition changes in such patients.

Prenatal nutritional constraint induces an altered metabolic phenotype in the offspring which in humans confers an increased risk of non-communicable disease. Feeding a protein-restricted (PR) diet to pregnant rats causes hypomethylation of specific gene promoters in the offspring and alters the phenotype. We investigated how altered epigenetic regulation of the hepatic glucocorticoid receptor (GR) 110 promoter is induced in the offspring. Rats were fed a control (180 g casein/kg) or a PR (90 g casein/kg) diet throughout pregnancy, and chow during lactation. Offspring were killed at postnatal day 34 (n 5 per maternal dietary group). Methylation-sensitive PCR showed that GR110 promoter methylation was 33 % lower (P < 0·001) and GR expression 84 % higher (P < 0·05) in the PR offspring. Reverse transcription–PCR showed that DNA methyltransferase-1 (Dnmt1) expression was 17 % lower (P < 0·05) in PR offspring, while Dnmt3a/b and methyl binding domain protein-2 expression was not altered. Thus hypomethylation of the GR110 promoter may result from lower capacity to methylate hemimethylated DNA during mitosis. Histone modifications which facilitate transcription were increased at the GR110 promoter (147–921 %, P < 0·001), while those that suppress methylation were decreased (54 %, P < 0·01) or similar to controls. In human umbilical cord (n 15), there was a 2-fold difference between the highest and lowest level of GR1-CTotal promoter methylation. Dnmt1, but not Dnmt3a, expression predicted 49 % (P = 0·003) of the variation in GR1-CTotal promoter methylation. These findings suggest that induction in the offspring of altered epigenetic regulation of the hepatic GR110 promoter, and hence metabolic phenotype, may be due to reduced Dnmt1 expression.

It is known that conjugated linoleic acid (CLA) feeding decreases body adiposity but the mechanisms involved are not clear. The aim of this study was to analyse whether alterations in uncoupling protein (UCP) expression in white and brown adipose tissues (WAT and BAT, respectively) and in skeletal muscle may be responsible for the effect of trans-10, cis-12 CLA on the size of body fat depots in hamsters. Animals were divided into three groups and fed an atherogenic diet with different amounts of trans-10, cis-12 CLA (0 control, 0·5, or 1 g/100 g diet) for 6 weeks. CLA feeding reduced adipose depot weights, but had no effect on body weight. Leptin mRNA expression decreased in both subcutaneous and perirenal WAT depots, in accordance with lower adiposity, whereas resistin mRNA expression was not changed. Animals fed CLA had lower UCP1 mRNA levels in BAT (both doses of CLA) and in perirenal WAT (the low dose), and lower UCP3 mRNA levels in subcutaneous WAT (the high dose). UCP2 mRNA expression in WAT was not significantly affected by CLA feeding. Animals fed the high dose of CLA showed increased UCP3 and carnitine palmitoyl transferase-I (CPT-I) mRNA expression levels in skeletal muscle. In summary, induction of UCP1 or UCP2 in WAT and BAT is not likely to be responsible for the fat-reduction action of CLA, but the increased expression of UCP3 in skeletal muscle, together with a higher expression of CPT-I, may explain the previously reported effects of dietary CLA in lowering adiposity and increasing fatty acid oxidation by skeletal muscle.

We investigated the combined effect of dietary supplementation with l-arginine, which is the precursor of NO, and pharmacological treatment with atorvastatin, which is a 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitor, on the development of atherosclerosis in homozygous Watanabe heritable hyperlipidaemic rabbits. Rabbits were fed either standard rabbit chow (group C; n 9) as control, a 1·5 % l-arginine diet (group A; n 9), standard rabbit chow plus atorvastatin (2·5 mg/kg per d) in drinking water (group S; n 8), or standard rabbit chow plus a 1·5 % l-arginine diet with atorvastatin (group SA; n 8). Blood was sampled at 2-week intervals. After 8 weeks (T8), the aorta was harvested for topographic and histological analysis. Only the SA group showed decreases in total area of lesions (21 %) and the area of abdominal lesions (44 %) compared with the control group (P = 0·019). Furthermore, plaques in the SA group were smaller and less thick than those observed in the S group. Unexpectedly, plasma nitrite + nitrate levels were not modified under either the l-arginine diet alone or under l-arginine plus atorvastatin. The present study is the first to demonstrate that diet supplementation with l-arginine associated with a statin (atorvastatin) is more efficient in reducing lesion size than treatment with l-arginine or a statin alone. This is a relatively novel therapeutic approach associating a macronutrient and a drug.

The methionine cycle and methyl group metabolism are implicated in the long-term programming of metabolism. Diets deficient in folic acid, methionine and choline have been fed to pregnant rats to examine the effects on amino acid metabolism, choline reserves and DNA methylation in dam and fetuses. Animals were fed folate-deficient, folate-deficient with low methionine, folate-deficient with low choline and folate-deficient, low-methionine, low-choline diets starting 2 weeks before mating. The dams and their fetuses were subsequently killed on day 21 of gestation for analysis. Diets low in methionine reduced fetal and maternal weight. Folate deficiency increased the concentrations of homocysteine, glycine, serine and threonine in the maternal plasma, and this was exacerbated by the low-methionine diets. The changes in the amino acid profile in the fetal serum were similar but less pronounced. This result suggests that fetal metabolism was less perturbed. Folate deficiency increased free choline in the maternal liver at the expense of phosphocholine stores. It has been suggested that a deficiency in methyl donors in the diet during pregnancy may impact on key methylation reactions, including the methylation of DNA. Despite widespread changes in the metabolism of choline and amino acids, there was no change in the global methylation of cytosine in DNA from either maternal or fetal livers. This suggests a more indirect mechanism in which gene–nutrient interactions modify the process of differential methylation during development

One approach to achieve weight loss and decrease both obesity and associated morbidities involves high-protein, low-carbohydrate (HPLC) diets. This study compares the impact on metabolic health of HPLC and high-protein, medium-carbohydrate (HPMC) diets offered to diet-induced obese (DIO) rats. Weanling male rats were fed either a 37 % fat diet (n 48) or stock pellets (n 12) for 22 weeks. Rats fed the 37 % fat diet accumulated more body fat (26·6 versus 14·8 % body weight, P < 0·001) compared with those on stock diet. The DIO rats had higher systolic blood pressure (+6·6 mmHg, P = 0·002), fasting insulin (+63 % P = 0·006) and areas under the glucose (+21 %, P < 0·001) and insulin (+81 %, P < 0·001) curves following an oral glucose tolerance test. DIO rats were then separated into four groups and offered for 8 weeks either: (1) the 37 % fat diet; (2) an HPLC or (3) HPMC diet; or (4) fed the 37 % fat diet to the intake of the HPMC group. Rats offered the 37 % fat or HPLC diets gained while those on HPMC lost body fat. Blood pressure was not altered by the dietary switch. Both HPLC and HPMC rats had lowered fasting insulin (P = 0·027) and improved homeostatic assessment (HOMA; P = 0·011) that was not different from those of stock animals. These improvements occurred despite differences in fat gain, and indicate that both weight loss and macronutrient intake can impact favourably on obesity-associated morbidities.

The aim was to investigate the effects of a 48 h period of fluid, energy or combined fluid and energy restriction on salivary IgA (s-IgA) responses at rest and after exercise. Thirteen healthy males (age 21 (sem 1) years) participated in four randomised 48 h trials. In the control trial participants received their estimated energy (12 154 (sem 230) kJ/d) and water (3912 (sem 140) ml/d) requirements. On fluid restriction (FR) participants received their energy requirements and 193 (sem 19) ml water/d to drink and on energy restriction (ER) participants received their water requirements and 1214 (sem 25) kJ/d. Fluid and energy restriction (F+ER) was a combination of FR and ER. After 48 h, participants performed a 30 min treadmill time trial (TT) followed by rehydration (0–2 h) and refeeding (2–6 h). Unstimulated saliva was collected at 0, 24 and 48 h, post-TT, and 2 and 6 h post-TT. Saliva flow rate (sflw) and s-IgA (ELISA) remained unchanged in control conditions and on ER. However, 48 h on FR decreased sflw (64 %) which most probably accounted for the increase in s-IgA concentration (P < 0·01). Despite a decrease in sflw (54 %), s-IgA concentration did not increase on F+ER, resulting in a decreased s-IgA secretion rate by 24 h (0 h: 20 (sem 2); 24 h: 12 (sem 2) μg/min; P < 0·01). Post-TT s-IgA secretion rate was not lower compared with 48 h on any trial. s-IgA secretion rate returned to within 0 h values by 6 h post-TT on F+ER. In conclusion, a 24–48 h period of combined F+ER decreased s-IgA secretion rate but normalisation occurred upon refeeding.

Lactic acid bacteria are probiotics widely used in functional food products, with a variety of beneficial effects reported. Recently, intense research has been carried out to provide insight into the mechanism of the action of probiotic bacteria. We have used gene array technology to map the pattern of changes in the global gene expression profile of the host caused by Lactobacillus administration. Affymetrix microarrays were applied to comparatively characterize differences in gene transcription in the distal ileum of normal microflora (NMF) and germ-free (GF) mice evoked by oral administration of two Lactobacillus strains used in fermented dairy products today – Lactobacillus paracasei ssp. paracasei F19 (L. F19) or Lactobacillus acidophilus NCFB 1748. We show that feeding either of the two strains caused very similar effects on the transcriptional profile of the host. Both L. F19 and L. acidophilus NCFB 1748 evoked a complex response in the gut, reflected by differential regulation of a number of genes involved in essential physiological functions such as immune response, regulation of energy homeostasis and host defence. Notably, the changes in intestinal gene expression caused by Lactobacillus were different in the mice raised under GF v. NMF conditions, underlying the complex and dynamic nature of the host-commensal relationship. Differential expression of an array of genes described in this report evokes novel hypothesis of possible interactions between the probiotic bacteria and the host organism and warrants further studies to evaluate the functional significance of these transcriptional changes on the metabolic profile of the host.

The immediate post-weaning period is often associated with gut malfunction and diarrhoea for young pigs. Administration of antimicrobials remains an effective way to control weaning diarrhoea but it remains unclear how they affect gut physiology and microbiology although this is a prerequisite for being able to devise better alternatives. Hence, for 7 d we treated pigs, weaned at 24 d of age, with a combination of amoxicillin (25 mg/kg feed and injection of 8·75 mg/kg body weight per 12 h) and ZnO (2·5 g/kg feed). The pigs treated with antimicrobials (n 11) showed no signs of gut malfunction at any time, whereas untreated weaned controls (n 11) developed clinical diarrhoea. The antimicrobial treatment resulted in a higher daily weight gain compared with weaned controls (101 v. − 44 g/d, P < 0·0001), whereas both groups had a similar degree of villous atrophy compared with unweaned 24-d-old controls (n 8; P < 0·05). The antimicrobial treatment gave a dramatic reduction in small intestinal microbial diversity, and specifically prevented tissue colonization with Escherichia coli compared with weaned controls. Further, the antimicrobial treatment improved amylase, trypsin and small intestinal aminopeptidase A and N activities (all P < 0·05). Specifically for the colon, the antimicrobial treatment was associated with reduced tissue weight ( − 23 %, P < 0·05), reduced concentration of SCFA (P < 0·05), and increased mucosal goblet cell area (P < 0·0001) compared with weaned controls. We conclude that the beneficial effects of antimicrobials are mediated not only through reduction in intestinal bacterial load, but also through a stimulation of protein digestive function and goblet cell density.

Although total plasma homocysteine (tHcy) has been extensively studied as a risk factor of CVD, longitudinal evidence on its association with mortality is scarce, especially among the elderly. The study cohort consisted of 215 subjects (eighty-eight male and 127 female), aged 60 years or older, recruited in fourteen elderly care institutions from Asturias (Spain). All participants were free of major chronic pathology and took no vitamin and/or mineral supplements. Baseline determinations included tHcy in plasma and folate, vitamin B12 and Se in serum. Survival analyses were performed by quintiles of these factors after 6 years (mean follow-up time 4·3 years) by means of Cox regression models. During follow-up time sixty participants died. tHcy above 16·7 μmol/l was associated with an increased risk of mortality in the sample (relative risk 2·30 (95 % CI 1·02, 5·17)). Among the nutritional determinants of tHcy evaluated, folate and Se were not predictive of death risk of the cohort, while vitamin B12 showed inconsistent results. Nevertheless, mortality was significantly lower at higher serum Se levels (upper quintile), but this effect was restricted to women. Higher tHcy in both sexes and lower serum Se in women were found to be independently associated with an increased risk of death in elderly subjects.

We investigated the effects of a high walnut diet and a high unsalted cashew nut diet on selected markers of the metabolic syndrome. In a randomized, parallel, controlled study design, sixty-four subjects having the metabolic syndrome (twenty-nine men, thirty-five women) with a mean age of 45 (sd 10) years and who met the selection criteria were all fed a 3-week run-in control diet. Hereafter, participants were grouped according to gender and age and then randomized into three groups receiving a controlled feeding diet including walnuts, or unsalted cashew nuts or no nuts for 8 weeks. Subjects were required to have lunch at the metabolic ward of the Nutrition Department of the North-West University (Potchefstroom Campus). Both the walnut and the unsalted cashew nut intervention diets had no significant effect on the HDL-cholesterol, TAG, total cholesterol, LDL-cholesterol, serum fructosamine, serum high-sensitivity C-reactive protein, blood pressure and serum uric acid concentrations when compared to the control diet. Low baseline LDL-cholesterol concentrations in the cashew nut group may have masked a possible nut-related benefit. Plasma glucose concentrations increased significantly (P = 0·04) in the cashew nut group compared to the control group. By contrast, serum fructosamine was unchanged in the cashew nut group while the control group had significantly increased (P = 0·04) concentrations of this short-term marker of glycaemic control. Subjects displayed no improvement in the markers of the metabolic syndrome after following a walnut diet or a cashew nut diet compared to a control diet while maintaining body weight.

In order to establish the biochemical basis for dietary interventions, we investigated the fatty acid composition of plasma lipid classes in patients with inactive inflammatory bowel disease. In this cross-sectional study thirty patients with ulcerative colitis (UC), twenty-one with Crohn disease (CD) and twenty-four controls were investigated (mean age: UC, 40·8 (sd 12·1); CD, 37·6 (sd 11·0); control, 31·5 (sd 8·4) years). Fatty acid composition of plasma lipids was determined by high-resolution capillary GLC. In plasma phospholipids, significantly higher values of eicosapentaenoic (20 : 5n-3), docosapentaenoic (22 : 5n-3) and γ-linolenic (18 : 3n-6) acids were found in control patients and patients with UC as compared to patients with CD [median % (weight by weight), control v. UC v. CD : 20 : 5n-3, 0·09 (interquartile range (IQR) 0·05) v. 0·14 (IQR 0·10) v. 0·16 (IQR 0·10), P < 0·05; 22 : 5n-3, 0·14 (IQR 0·10) v. 0·27 (IQR 0·16) v. 0·31 (IQR 0·10), P < 0·001; 18 : 3n-6, 0·02 (IQR 0·02) v. 0·03 (IQR 0·02) v. 0·05 (IQR 0·03), P < 0·05]. When compared to the control, values of the principal n-3 and n-6 long-chain PUFA, arachidonic acid (20 : 4n-6) and DHA (22 : 6n-3) were significantly higher in patients with UC but not in patients with CD [median % (w/w), UC v. control: 20 : 4n-6, 8·43 (IQR 3·23) v. 6·92 (IQR 2·96), P < 0·05; 22 : 6n-3, 1·22 (IQR 0·56) v. 0·73 (IQR 0·39), P < 0·05]. As seen there are considerable differences between the long-chain PUFA status of patients suffering from UC or CD. The data obtained in the present study do not support the concept of eicosapentaenoic acid or DHA deficiency in patients with either UC or CD.

Barley, like oats, is a rich source of the soluble fibre β-glucan, which has been shown to significantly lower LDL-cholesterol (LDL-C). However, barley foods have been less widely studied. Therefore, we evaluated the LDL-C-lowering effect of a concentrated barley β-glucan (BBG) extract as a vehicle to deliver this potential health benefit of barley. In a 10-week blinded controlled study, subjects were randomized to one of four treatment groups or control. Treatment groups included either high molecular weight (HMW) or low molecular weight (LMW) BBG at both 3 and 5 g doses. Treatment was delivered twice per day with meals in the form of two functional food products: a ready-to-eat cereal and a reduced-calorie fruit juice beverage. Levels of total cholesterol, LDL-C, HDL-cholesterol (HDL-C), and TAG were determined at baseline and after 6 weeks of treatment. The study group comprised 155 subjects. All treatments were well tolerated and after 6 weeks of treatment the mean LDL-C levels fell by 15 % in the 5 g HMW group, 13 % in the 5 g LMW group and 9 % in both the 3 g/d groups, versus baseline. Similar results were observed for total cholesterol. HDL-C levels were unchanged by treatment. Concentrated BBG significantly improves LDL-C and total cholesterol among moderately dyslipidaemic subjects. Food products containing concentrated BBG should be considered an effective option for improving blood lipids.

Under-reporting (UR) of energy intake (EI) by self-reported dietary methods is well-documented but the methods used to estimate UR in population-based studies commonly assume a sedentary lifestyle. We compared estimated UR using individualised estimates of energy requirements with a population cut-off based on minimum energy needs. UR was estimated for 1551 adults aged 19–64 years enrolled in the National Diet and Nutrition Survey. Physical activity diaries and 7 d weighed dietary records were completed concurrently. Mean daily EI (kJ/d) was calculated from the dietary records. Reported physical activity was used to assign each subject's activity level, and then to calculate estimated energy requirements (EER) from published equations. UR was calculated both as EER – EI with an adjustment for daily EER and EI variation, and also by a population method. By the individual method UR was approximately 27 % of energy needs in men and 29 % in women, with 75 % of men and 77 % of women classified as under-reporters; by the population method 80 and 88 % were classified as under-reporters respectively. When subjects who reported their eating being affected by dieting or illness during dietary recording were excluded, UR was 25 % of energy needs in both sexes. UR was higher in overweight and obese men and women compared with their lean counterparts (P < 0·001). UR of EI must be considered in dietary surveys. The EER method allows UR to be quantified and takes into account an individual's activity level. Measures of physical activity and questions to identify under-eating during dietary recording may help to evaluate secular trends in UR.