Abstract
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)).
Highlights
Metabolomics has considerable potential as an analytical tool to rapidly obtain information on the metabolic fingerprints/ metabolites of individuals
The analysis of the pooled plasma QC sample revealed that a high proportion (∼87%) of the metabolites had an interplate coefficient of variation (CV) < 20%, with 68 metabolites exhibiting CVs < 10% (Figure S1)
Our results indicate that metabolite levels measured using a targeted LC-MS/MS metabolomics platform resulted in highly reproducible data in a healthy adult population over a 4 month period
Summary
Metabolomics has considerable potential as an analytical tool to rapidly obtain information on the metabolic fingerprints/ metabolites of individuals. These metabolites reflect the multiple influences of genetics, the microbiome, and environmental factors, such as exercise, pollutants, or diet,[1,2] and give detailed information related to metabolic pathways and biological processes. The advancement of analytical technologies in the field of metabolomics has made it possible to perform high-throughput metabolite identification and quantification in biological specimens. In the context of nutritional epidemiology, metabolomics offers great promise, with many applications for both targeted and untargeted approaches. Targeted metabolomic platforms offer the possibility of identification of risk biomarkers and understanding the impact of diet on metabolic pathways
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