Aifric O'Sullivan

Dietary intake patterns are reflected in metabolomic profiles: potential role in dietary assessment studies

BACKGROUND It has been suggested that metabolomics could play a role in dietary assessment and identification of novel biomarkers of dietary intake. OBJECTIVE This study examined the link between habitual dietary patterns and metabolomic profiles. DESIGN A total of 160 volunteers participated in a double-blind, randomized, placebo-controlled dietary intervention. We collected biofluids and recorded 3-d food diaries. Food data were reduced to 33 food groups, and a k-means cluster analysis was performed to identify dietary patterns. (1)H Nuclear magnetic resonance (NMR) spectra were acquired for plasma and urine samples, and gas chromatography was used for plasma fatty acid profiling. RESULTS Cluster analysis identified 3 distinct dietary patterns on the basis of the energy contribution of different food groups. Dietary clusters were reflected in plasma fatty acid profiles and in metabolomic data. (1)H NMR spectra of urine allowed the identification of metabolites associated with different dietary patterns. Several of the metabolites identified were linked to the intake of specific food groups; in particular, there was a positive association between O-acetylcarnitine and phenylacetylglutamine and red-meat and vegetable intakes, respectively. CONCLUSIONS Habitual dietary patterns are shown in metabolomic data. This approach successfully identified potential biomarkers of red-meat and vegetable intakes.

Biochemical and metabolomic phenotyping in the identification of a vitamin D responsive metabotype for markers of the metabolic syndrome

SCOPE Metabolic phenotyping promises to be a useful tool in human intervention studies. This study examined whether metabolic phenotyping could identify responders to vitamin D supplementation in terms of the metabolic syndrome. METHODS AND RESULTS In a double-blind, randomised placebo-controlled dietary intervention subjects were assigned to receive 15 μg vitamin D(3) or placebo daily. Serum 25-hydroxyvitamin D (25(OH)D) and biochemical markers of the metabolic syndrome were measured at baseline and following the 4-wk intervention. k-means clustering and (1) H-NMR metabolomic analysis were used to explore responsive phenotypes. Vitamin D supplementation significantly increased serum 25(OH)D to an endpoint concentration of 78.1 ± 20.0 nmol/L (p<0.001). There was no effect of supplementation on the measured markers of the metabolic syndrome. k-means cluster analysis based on 13 biochemical markers of the metabolic syndrome and 25(OH)D concentrations revealed five discrete biomarker clusters. One of these clusters, characterised by lower serum 25(OH)D and higher levels of adipokines, showed significant responses in insulin (15% decrease), homestatic model assessment scores (19% decrease) and c-reactive protein (54% decrease). Metabolomic analysis revealed further changes and the extent of change in serum vitamin D correlated negatively with changes in glucose. CONCLUSION Overall, metabolic phenotyping revealed a phenotype that was responsive to vitamin D supplementation.

Six weeks of a polarized training-intensity distribution leads to greater physiological and performance adaptations than a threshold model in trained cyclists

This study was undertaken to investigate physiological adaptation with two endurance-training periods differing in intensity distribution. In a randomized crossover fashion, separated by 4 wk of detraining, 12 male cyclists completed two 6-wk training periods: 1) a polarized model [6.4 (±1.4 SD) h/wk; 80%, 0%, and 20% of training time in low-, moderate-, and high-intensity zones, respectively]; and 2) a threshold model [7.5 (±2.0 SD) h/wk; 57%, 43%, and 0% training-intensity distribution]. Before and after each training period, following 2 days of diet and exercise control, fasted skeletal muscle biopsies were obtained for mitochondrial enzyme activity and monocarboxylate transporter (MCT) 1 and 4 expression, and morning first-void urine samples were collected for NMR spectroscopy-based metabolomics analysis. Endurance performance (40-km time trial), incremental exercise, peak power output (PPO), and high-intensity exercise capacity (95% maximal work rate to exhaustion) were also assessed. Endurance performance, PPOs, lactate threshold (LT), MCT4, and high-intensity exercise capacity all increased over both training periods. Improvements were greater following polarized rather than threshold for PPO [mean (±SE) change of 8 (±2)% vs. 3 (±1)%, P < 0.05], LT [9 (±3)% vs. 2 (±4)%, P < 0.05], and high-intensity exercise capacity [85 (±14)% vs. 37 (±14)%, P < 0.05]. No changes in mitochondrial enzyme activities or MCT1 were observed following training. A significant multilevel, partial least squares-discriminant analysis model was obtained for the threshold model but not the polarized model in the metabolomics analysis. A polarized training distribution results in greater systemic adaptation over 6 wk in already well-trained cyclists. Markers of muscle metabolic adaptation are largely unchanged, but metabolomics markers suggest different cellular metabolic stress that requires further investigation.

Metabolomic phenotyping validates the infant rhesus monkey as a model of human infant metabolism.

Objectives: Rhesus macaque monkeys are widely used as models for human physiology and behavior. They are particularly suited for studies on infant nutrition and metabolism; however, few studies have directly compared their metabolic or microbiological phenotypes. The aim of the present study was to compare the metabolomic profiles and microbiome of milk from human and rhesus mothers, and the metabolomic profiles of urine and serum from human and rhesus infants to establish the value of this model for human nutrition research. Methods: Milk samples were collected from rhesus and human mothers at similar stages of lactation. Urine and serum samples were collected from breast-fed rhesus and human infants. 1H nuclear magnetic resonance spectra were acquired for all samples and metabolites were identified and quantified using targeted profiling techniques. The microbial community structure of milk was examined using 16S rRNA gene sequencing. Results: An identical set of metabolites was identified in the urine and serum profiles from human and rhesus infants. In urine, 65% of the metabolites were present at similar concentrations, whereas ∼40% were similar in serum. The gross composition of human and rhesus milk was comparable, including the overall microbial community at both the phylum and order level; however, some oligosaccharides found in human milk were not present in monkey milk. Conclusions: Comparison of the milk microbiome and urine, serum, and milk metabolome of rhesus macaques and humans has revealed substantial similarities that provide unique biological information highlighting the significance of rhesus macaques as a model for infant nutrition and developmental research.

The Influence of Early Infant-Feeding Practices on the Intestinal Microbiome and Body Composition in Infants.

Despite many years of widespread international recommendations to support exclusive breastfeeding for the first six months of life, common hospital feeding and birthing practices do not coincide with the necessary steps to support exclusive breastfeeding. These common hospital practices can lead to the infant receiving formula in the first weeks of life despite mothers’ dedication to exclusively breastfeed. Consequently, these practices play a role in the alarmingly high rate of formula-feeding worldwide. Formula-feeding has been shown to alter the infant gut microbiome in favor of proinflammatory taxa and increase gut permeability and bacterial load. Furthermore, several studies have found that formula-feeding increases the risk of obesity in later childhood. While research has demonstrated differences in the intestinal microbiome and body growth between exclusively breast versus formula-fed infants, very little is known about the effects of introducing formula to breastfed infants either briefly or long term on these outcomes. Understanding the relationships between mixed-feeding practices and infant health outcomes is complicated by the lack of clarity in the definition of mixed-feeding as well as the terminology used to describe this type of feeding in the literature. In this commentary, we highlight the need for hospitals to embrace the 10 steps of the Baby Friendly Hospital Initiative developed by UNICEF and the WHO for successful breastfeeding. We present a paucity of studies that have focused on the effects of introducing formula to breastfed infants on the gut microbiome, gut health, growth, and body composition. We make the case for the need to conduct well-designed studies on mixed-feeding before we can truly answer the question: how does brief or long-term use of formula influence the health benefits of exclusive breastfeeding?

Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40–65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

Effect of supplementation with vitamin D3 on glucose production pathways in human subjects

SCOPE Research reports suggest that vitamin D affects glucose and insulin metabolism; however, the exact mechanisms are unclear. ²H NMR analysis of monoacetone glucose (MAG) after tracer administration provides a non-invasive method of profiling hepatic glucose metabolism. This study examined the effects of supplementation with vitamin D₃ on contribution of glycogenolysis to glucose production. METHODS AND RESULTS Tracer administration and biofluid collections were performed with eight healthy females before and following a 4-wk vitamin D₃ administration period. Following an overnight fast subjects ingested deuterated water and acetaminophen. Full void urine samples were collected after 4 h. ²H NMR spectra of urinary monoacetone glucose were acquired to determine the contribution of glycogenolysis to glucose production. The mean contribution of glycogenolysis to glucose production was 60±13%. Supplementation with vitamin D₃ had no effect on hepatic glucose production. Regression analysis revealed a significant relationship between carbohydrate intake and the contribution of glycogenolysis (β=0.914, p=0.004). CONCLUSION In conclusion, we saw no changes in the percentage contribution of glycogenolysis following supplementation with vitamin D₃. The reproducibility of our results and the non-invasive nature of the method highlight the potential for this method in assessing mechanistic modes of action in future nutritional interventions.

Effect of probiotic and vitamin D supplementation on markers of vitamin D status and bone turnover in healthy adults

There is some in vitro evidence that probiotic bacteria may influence Ca uptake in the intestine, possibly through an interaction with vitamin D endocrine system, with potential benefit for bone turnover. However, the effect of probiotic bacteria on bone turnover has not been investigated in human subjects. The objective of the present study was to examine the effect of 4-week supplementation with probiotics and vitamin D on serum 25-hydroxyvitamin D (S-25(OH)D), parathyroid hormone (PTH) and biochemical markers of bone turnover in healthy adults. In a randomised double-blind placebo-controlled trial conducted in Dublin and Cork, 147 subjects aged between 18–63 years (seventy men and seventy-seven women) were randomised to receive daily for 4 weeks at two different intervention periods (November 2007 and April 2008): 15mg cholecalciferol and 1 · 10 Lactobacillus Salivarius, UCC 118 (probiotic); 15mg cholecalciferol and probiotic placebo; cholecalciferol placebo and probiotic; cholecalciferol placebo and probiotic placebo. S-25(OH)D concentrations and serum concentrations of PTH, osteocalcin (OC), bone-specific alkaline phosphatase (BAP) as well as urinary concentrations of N-telopeptides of type I collagen (NTx) were assessed at baseline and post intervention using commercially-available ELISA kits. One-way between-groups analysis of covariance (ANCOVA) was used to examine the effect of treatment group on post-intervention biochemical variables while including age, gender, season of blood draw and baseline biochemical concentrations as covariates.

21st century toolkit for optimizing population health through precision nutrition

ABSTRACT Scientific, technological, and economic progress over the last 100 years all but eradicated problems of widespread food shortage and nutrient deficiency in developed nations. But now society is faced with a new set of nutrition problems related to energy imbalance and metabolic disease, which require new kinds of solutions. Recent developments in the area of new analytical tools enable us to systematically study large quantities of detailed and multidimensional metabolic and health data, providing the opportunity to address current nutrition problems through an approach called Precision Nutrition. This approach integrates different kinds of “big data” to expand our understanding of the complexity and diversity of human metabolism in response to diet. With these tools, we can more fully elucidate each individuals unique phenotype, or the current state of health, as determined by the interactions among biology, environment, and behavior. The tools of precision nutrition include genomics, metabolomics, microbiomics, phenotyping, high-throughput analytical chemistry techniques, longitudinal tracking with body sensors, informatics, data science, and sophisticated educational and behavioral interventions. These tools are enabling the development of more personalized and predictive dietary guidance and interventions that have the potential to transform how the public makes food choices and greatly improve population health.

The effects of probiotic supplementation on gut microbiota composition, immunological and biochemical markers in healthy volunteers

A. O’Connor, A. O’Sullivan, S. Kaluskar, B. Mion, J. Marchesi, K. Cashman, A. Flynn, F. Shanahan, L. Brennan and M. J. Gibney UCD Institute of Food and Health, School of Agriculture, Food Science and Veterinary Medicine, Veterinary Science Centre, Belfield, Dublin 4, Republic of Ireland, and Alimentary Pharmabiotic Centre and Department of Food & Nutritional Sciences, University College Cork, National University of Ireland, Cork, Republic of Ireland