The type and quantity of dietary fat and carbohydrate alter faecal microbiome and short-chain fatty acid excretion in a metabolic syndrome 'at-risk' population.

INTRODUCTION AND OBJECTIVES: An obese-type human microbiota with an increased Firmicutes:Bacteroidetes ratio has been described that may link the gut microbiome with obesity and metabolic syndrome (MetS) development. Dietary fat and carbohydrate are modifiable risk factors that may impact on MetS by altering the human microbiome composition. We determined the effect of the amount and type of dietary fat and carbohydrate on faecal bacteria and short chain fatty acid (SCFA) concentrations in people 'at risk' of MetS. DESIGN: A total of 88 subjects at increased MetS risk were fed a high saturated fat diet (HS) for 4 weeks (baseline), then randomised onto one of the five experimental diets for 24 weeks: HS; high monounsaturated fat (MUFA)/high glycemic index (GI) (HM/HGI); high MUFA/low GI (HM/LGI); high carbohydrate (CHO)/high GI (HC/HGI); and high CHO/low GI (HC/LGI). Dietary intakes, MetS biomarkers, faecal bacteriology and SCFA concentrations were monitored. RESULTS: High MUFA diets did not affect individual bacterial population numbers but reduced total bacteria and plasma total and LDL-cholesterol. The low fat, HC diets increased faecal Bifidobacterium (P=0.005, for HC/HGI; P=0.052, for HC/LGI) and reduced fasting glucose and cholesterol compared to baseline. HC/HGI also increased faecal Bacteroides (P=0.038), whereas HC/LGI and HS increased Faecalibacterium prausnitzii (P=0.022 for HC/HGI and P=0.018, for HS). Importantly, changes in faecal Bacteroides numbers correlated inversely with body weight (r=-0.64). A total bacteria reduction was observed for high fat diets HM/HGI and HM/LGI (P=0.023 and P=0.005, respectively) and HS increased faecal SCFA concentrations (P<0.01). CONCLUSION: This study provides new evidence from a large-scale dietary intervention study that HC diets, irrespective of GI, can modulate human faecal saccharolytic bacteria, including bacteroides and bifidobacteria. Conversely, high fat diets reduced bacterial numbers, and in the HS diet, increased excretion of SCFA, which may suggest a compensatory mechanism to eliminate excess dietary energy.

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 multi-factorial 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.

Impact of menstrual cycle phase on insulin sensitivity measures and fasting lipids.

There is evidence to suggest that insulin sensitivity may vary in response to changes in sex hormone levels. However, the results of human studies designed to investigate changes in insulin sensitivity through the menstrual cycle have proved inconclusive. The aims of this study were to 1) evaluate the impact of menstrual cycle phase on insulin sensitivity measures and 2) determine the variability of insulin sensitivity measures within the same menstrual cycle phase. A controlled observational study of 13 healthy premenopausal women, not taking any hormone preparation and having regular menstrual cycles, was conducted. Insulin sensitivity (Si) and glucose effectiveness (Sg) were measured using an intravenous glucose tolerance test (IVGTT) with minimal model analysis. Additional surrogate measures of insulin sensitivity were calculated (homoeostasis model for insulin resistance [HOMA IR], quantitative insulin-to-glucose check index [QUICKI] and revised QUICKI [rQUICKI]), as well as plasma lipids. Each woman was tested in the luteal and follicular phases of her menstrual cycle, and duplicate measures were taken in one phase of the cycle. No significant differences in insulin sensitivity (measured by the IVGTT or surrogate markers) or plasma lipids were reported between the two phases of the menstrual cycle or between duplicate measures within the same phase. It was concluded that variability in measures of insulin sensitivity were similar within and between menstrual phases.

The gut microbiota and lipid metabolism: implications for human health and coronary heart disease.

Coronary heart disease (CHD) is the leading cause of mortality in Western societies, affecting about one third of the population before their seventieth year. Over the past decades modifiable risk factors of CHD have been identified, including smoking and diet. These factors when altered can have a significant impact on an individuals' risk of developing CHD, their overall health and quality of life. There is strong evidence suggesting that dietary intake of plant foods rich in fibre and polyphenolic compounds, effectively lowers the risk of developing CHD. However, the efficacy of these foods often appears to be greater than the sum of their recognised biologically active parts. Here we discuss the hypothesis that beneficial metabolic and vascular effects of dietary fibre and plant polyphenols are due to an up regulation of the colon-systemic metabolic axis by these compounds. Fibres and many polyphenols are converted into biologically active compounds by the colonic microbiota. This microbiota imparts great metabolic versatility and dynamism, with many of their reductive or hydrolytic activities appearing complementary to oxidative or conjugative human metabolism. Understanding these microbial activities is central to determining the role of different dietary components in preventing or beneficially impacting on the impaired lipid metabolism and vascular dysfunction that typifies CHD and type II diabetes. This approach lays the foundation for rational selection of health promoting foods, rational target driven design of functional foods, and provides an essential thus-far, overlooked, dynamic to our understanding of how foods recognised as "healthy" impact on the human metabonome.

Maternal micronutrient status and decreased growth of Zambian infants born during and after the maize price increases resulting from the southern African drought of 2001-2002.

OBJECTIVE: To investigate the effects on maternal micronutrient status and infant growth of the increased maize prices that resulted from the southern African drought of 2001-2002. DESIGN: Longitudinal cohort study. SETTING: A maternal and child health clinic in Lusaka, Zambia. SUBJECTS: Maternal and infant health and nutrition data and maternal plasma were being collected for a study of breast-feeding and postpartum health. Samples and data were analysed according to whether they were collected before (June to December 2001), during (January 2002 to April 2003) or after (May 2003 to January 2004) the period of increased maize price. Season and maternal HIV status were controlled for in analyses. RESULTS: Maize price increases were associated with decreased maternal plasma vitamin A during pregnancy (P = 0.028) and vitamin E postpartum (P = 0.042), with the lowest values among samples collected after May 2003 (vitamin A: 0.96 micromol l(-1), 95% confidence interval (CI) 0.84-1.09, n = 38; vitamin E: 30.8 micromol mmol(-1) triglycerides, 95% CI 27.2-34.8, n = 64) compared with before January 2002 (vitamin A: 1.03 micromol l(-1), 95% CI 0.93-1.12, n = 104; vitamin E: 38.9 micromol mmol(-1) triglycerides, 95% CI 34.5-43.8, n = 47). There were no significant effects of sampling date on maternal weight, haemoglobin or acute-phase proteins and only marginal effects on infant weight. Infant length at 6 and 16 weeks of age decreased progressively throughout the study (P-values for time of data collection were 0.51 at birth, 0.051 at 6 weeks and 0.026 at 16 weeks). CONCLUSIONS: The results show modest effects of the maize price increases on maternal micronutrient status. The most serious consequence of the price increases is likely to be the increased stunting among infants whose mothers experienced high maize prices while pregnant. During periods of food shortages it might be advisable to provide micronutrient supplements even to those who are less food-insecure.

Fetal plasma testosterone correlates positively with cortisol.

BACKGROUND: Fetal exposure to testosterone has been implicated in programming childhood behaviour, but little is known about the determinants of fetal testosterone concentrations. AIMS: To investigate the relation between fetal testosterone and maternal and fetal cortisol. METHODS: Clinically indicated blood samples taken from 44 human fetuses (mean gestational age 27 weeks, range 15-38), together with paired maternal samples, were analysed for testosterone and cortisol concentrations. RESULTS: Male fetuses had significantly higher concentrations of testosterone than females. Female but not male fetal concentrations rose significantly with gestational age. Fetal testosterone correlated positively with both fetal cortisol and maternal testosterone concentrations. Multiple regression showed that maternal testosterone and fetal cortisol were independently correlated with fetal plasma testosterone in both sexes. CONCLUSION: Unlike the norm in the adult, where testosterone production is often inhibited by cortisol, in the fetus there is a positive link between the two.

Human fetal and maternal corticotrophin releasing hormone responses to acute stress.

OBJECTIVES: To study the effect of acute stress, caused by intrauterine needling at the intrahepatic vein (IHV), on fetal plasma concentrations of corticotrophin releasing hormone (CRH), and to compare paired fetal and maternal samples for CRH concentration to determine the extent of their joint control. DESIGN: Venous blood samples were obtained from fetuses (gestational age 17-38 weeks) undergoing fetal blood sampling (n = 29) or intrauterine transfusion (n = 17) through either the IHV or the placental cord insertion (PCI). SETTING: The Centre for Fetal Care, Queen Charlotte's and Chelsea Hospital, London, UK. PATIENTS: Pregnant women undergoing clinically indicated fetal blood sampling or intrauterine blood/platelet transfusion. RESULTS: Fetal plasma cortisol increased with intrahepatic vein transfusion (mean (SD) cortisol response Delta64.7 (54.5) nmol/l; p < 0.0001, n = 11), and fetal corticotrophin concentrations were higher after IHV (n = 7) than PCI needling (n = 6). Neither fetal nor maternal plasma CRH increased after IHV transfusion. Fetal CRH levels did not rise with gestation, whereas maternal CRH levels did (r = 0.58; n = 36; p < 0.0001). There was a modest correlation between paired maternal and fetal values (r = 0.36; n = 36; p = 0.03). CONCLUSIONS: Acute fetal stress, caused by IHV needling of the fetal abdomen, resulted in hypothalamic-pituitary-adrenal axis activation, as shown by a rise in fetal cortisol and corticotrophin. However, it did not result in measurable CRH release into fetal plasma. This suggests that fetal plasma CRH is not derived from the hypophyseal-portal circulation, but from another source, presumably the placenta.

Effect of direct fetal opioid analgesia on fetal hormonal and hemodynamic stress response to intrauterine needling.

BACKGROUND: Whether the fetus can experience pain remains controversial. During the last half of pregnancy, the neuroanatomic connections for nociception are in place, and the human fetus mounts sizable stress responses to physical insults. Analgesia has been recommended for intrauterine procedures or late termination, but without evidence that it works. The authors investigated whether fentanyl ablates the fetal stress response to needling using the model of delayed interval sampling during intrahepatic vein blood sampling and transfusion in alloimmunized fetuses undergoing intravascular transfusion between 20 and 35 weeks. METHODS: Intravenous fentanyl (10 microg/kg estimated fetal weight x 1.25 placental correction) was given once at intrahepatic vein transfusion in 16 fetuses, and changes (posttransfusion - pretransfusion) in beta endorphin, cortisol, and middle cerebral artery pulsatility index were compared with intrahepatic vein transfusions without fentanyl and with control transfusions at the placental cord insertion. RESULTS: Fentanyl reduced the beta endorphin (mean difference in changes, -70.3 pg/ml; 95% confidence interval, -121 to -19.2; P = 0.02) and middle cerebral artery pulsatility index response (mean difference, 0.65; 95% confidence interval, 0.26-1.04; P = 0.03), but not the cortisol response (mean difference, -10.9 ng/ml, 95% confidence interval, -24.7 to 2.9; P = 0.11) in fetuses who had paired intrahepatic vein transfusions with and without fentanyl. Comparison with control fetuses transfused without fentanyl indicated that the beta endorphin and cerebral Doppler response to intrahepatic vein transfusion with fentanyl approached that of nonstressful placental cord transfusions. CONCLUSIONS: The authors conclude that intravenous fentanyl attenuates the fetal stress response to intrahepatic vein needling.

Umbilical cortisol levels as an indicator of the fetal stress response to assisted vaginal delivery.

OBJECTIVES: While it is well established that delivery by elective caesarean section is less stressful for the fetus than normal vaginal delivery, little attention has been paid to the effect on the baby of an assisted delivery. STUDY DESIGN: We examined cortisol levels in venous cord blood from seven babies born by forceps, 10 by ventouse extraction, 28 by unassisted normal vaginal delivery, and 12 born by elective caesarean. Paired maternal bloods were taken immediately after delivery. RESULTS: Cord blood cortisol values were significantly different in the different groups (one-way ANOVA, P < 0.0001). The forceps group had the highest values and the caesarean group the lowest; both were different from the normal vaginal delivery group (P=0.019 and P=0.046, respectively). There was no effect of length of labour, or method of pain relief on cortisol levels. Maternal values were similar in the different groups, confirming that the differences observed derived from the fetus. CONCLUSIONS: There is increasing evidence that the stress experienced by the fetus or neonate can have long-term effects on the function of the hypothalamic-pituitary-adrenal axis in later life. We speculate that the stress caused by some assisted deliveries may contribute to this.

Fetal hypothalamic-pituitary-adrenal stress responses to invasive procedures are independent of maternal responses.

Paired fetal and maternal samples were obtained, at fetal blood sampling and intrauterine transfusion, to study hypothalamic-pituitary-adrenal stress responses. This confirmed that the fetus mounts an hypothalamic-pituitary-adrenal stress response to transfusion via the intrahepatic vein, which involves piercing the fetal trunk, but not to transfusion via the placental cord insertion [mean cortisol response via intrahepatic vein delta = 52.6 nmol/L, 95% CI (25.3-79.9), P = 0.001; mean beta-endorphin response delta =106 pg/mL, 95% CI (45.3-167), P = 0.002]. Baseline maternal fetal ratios were 13 [95% CI (10.7-15.2)] for cortisol and 0.8 [95% CI (0.5-1.0)] for beta-endorphin. The novel findings were: 1) that the fetal responses were independent of those of the mother, which did not change during transfusion at either site; 2) that there was a correlation between baseline fetal and maternal cortisol levels (r = 0.58, n = 51, P < 0.0001) but not between baseline fetal and maternal ss-endorphin levels, suggesting cortisol transfer across the placenta, rather than joint control by placental CRH; and 3) that fetal beta-endorphin responses were apparent from 18 weeks gestation and independent of gestational age, whereas fetal cortisol responses were apparent from 20 weeks gestation and were dependent on gestational age (y = -91.4 + 5.08x, r = 0.51; n = 16; P = 0.04; CI for slope, 0.16-10.0), consistent with the maturation of the fetal pituitary before the fetal adrenal.

Maternal stress in pregnancy and its effect on the human foetus: an overview of research findings.

There is evidence from human studies that anxiety or stress during pregnancy can affect birth outcome, causing babies to be born earlier and possibly smaller for gestational age. There is also some suggestive evidence for longer-term behavioural problems. Animal studies indicate that antenatal stress does have a long-term effect on the behaviour of the offspring, including a hyper-responsive hypothalamo-pituitary -adrenal axis. The human foetus can mount an independent stress response from mid-gestation. Two possible mechanisms have been demonstrated by which maternal stress or anxiety may affect the human foetus, the passage of cortisol across the placenta, and an impairment of blood flow through the maternal uterine arteries.

Pain and stress in the human fetus.

Invasive diagnostic and therapeutic techniques are increasingly applied to the fetus. It is not known if the fetus feels pain during such procedures, but the fetus does mount significant stress hormonal and circulatory changes in response to these from 18-20 weeks. Perinatal stress may have long-term neurodevelopmental implications. During open fetal surgery, maternal general anaesthesia provides fetal anaesthesia. However, in closed procedures, fetal analgesia presents difficulties. The optimal drug, dose, and route of administration remain to be determined.