Targeted Metabolomic Approach to Assess the Reproducibility of Plasma Metabolites over a Four Month Period in a Free-Living Population.

Metabolomics is increasingly applied to investigate diet-disease associations in nutrition research. However, studies of metabolite reproducibility are limited, which could hamper their use within epidemiologic studies. The objective of this study was to evaluate the metabolite reproducibility during 4 months in a free-living population. In the A-DIET Confirm study, fasting plasma and dietary data were collected once a month for 4 months. Metabolites were measured using liquid chromatography tandem mass spectrometry, and their reproducibility was estimated using the intraclass correlation coefficient (ICC). Regularized canonical correlation analysis (rCCA) was employed to examine the diet-metabolite associations. In total, 138 metabolites were measured, and median ICC values of 0.49 and 0.65 were found for amino acids and biogenic amines, respectively. Acylcarnitines, lysophosphatidylcholines, phosphatidylcholines, and sphingomyelins had median ICC values of 0.69, 0.66, 0.63, and 0.63, respectively. The median ICC for all metabolites was 0.62, and 54% of metabolites had ICC values ≥0.60. Additionally, the rCCA heat map revealed positive correlations between dairy/meat intake and specific lipids. In conclusion, more than half of the metabolites demonstrated good to excellent reproducibility. A single measurement per subject could appropriately reflect the metabolites' long-term concentration levels and may also be sufficient for assessing disease risk in epidemiologic studies. The study data are deposited in MetaboLights (MTBLS3428 (www.ebi.ac.uk/metabolights)).

Classifying Individuals Into a Dietary Pattern Based on Metabolomic Data.

SCOPE: The objectives are to develop a metabolomic-based model capable of classifying individuals into dietary patterns and to investigate the reproducibility of the model. METHODS AND RESULTS: K-means cluster analysis is employed to derive dietary patterns using metabolomic data. Differences across the dietary patterns are examined using nutrient biomarkers. The model is used to assign individuals to a dietary pattern in an independent cohort, A-DIET Confirm (n = 175) at four time points. The stability of participants to a dietary pattern is assessed. Four dietary patterns are derived: moderately unhealthy, convenience, moderately healthy, and prudent. The moderately unhealthy and convenience patterns has lower adherence to the alternative healthy eating index (AHEI) and the alternative mediterranean diet score (AMDS) compared to the moderately healthy and prudent patterns (AHEI = 24.5 and 22.9 vs 26.7 and 28.4, p < 0.001). The dietary patterns are replicated in A-DIET Confirm, with good reproducibility across four time points. The stability of participants' dietary pattern membership ranged from 25.0% to 61.5%. CONCLUSION: The multivariate model classifies individuals into dietary patterns based on metabolomic data. In an independent cohort, the model classifies individuals into dietary patterns at multiple time points furthering the potential of such an approach for nutrition research.

Radiation-induced Bystander Effect (RIBE) alters mitochondrial metabolism using a human rectal cancer ex vivo explant model.

Locally advanced rectal cancer is treated with neoadjuvant-chemoradiotherapy, however only 22% of patients achieve a complete response. Resistance mechanisms are poorly understood. Radiation-induced Bystander Effect (RIBE) describes the effect of radiation on neighbouring unirradiated cells. We investigated the effects of ex vivo RIBE-induction from normal and rectal cancer tissue on bystander cell metabolism, mitochondrial function and metabolomic profiling. We correlated bystander events to patient clinical characteristics. Ex vivo RIBE-induction caused metabolic alterations in bystander cells, specifically reductions in OXPHOS following RIBE-induction in normal (p = 0.01) and cancer tissue (p = 0.03) and reduced glycolysis following RIBE-induction in cancer tissue (p = 0.01). Visceral fat area correlated with glycolysis (p = 0.02) and ATP production (p = 0.03) following exposure of cells to TCM from irradiated cancer biopsies. Leucine levels were reduced in the irradiated cancer compared to the irradiated normal secretome (p = 0.04). ROS levels were higher in cells exposed to the cancer compared to the normal secretome (p = 0.04). RIBE-induction ex vivo causes alterations in the metabolome in normal and malignant rectal tissue along with metabolic alterations in bystander cellular metabolism. This may offer greater understanding of the effects of RIBE on metabolism, mitochondrial function and the secreted metabolome.