Identification and Reproducibility of Urinary Metabolomic Biomarkers of Habitual Food Intake in a Cross-Sectional Analysis of the Cancer Prevention Study-3 Diet Assessment Sub-Study

Abstract

Previous cross-sectional metabolomics studies have identified many potential dietary biomarkers, mostly in blood. Few studies examined urine samples although urine is preferred for dietary biomarker discovery. Furthermore, little is known regarding the reproducibility of urinary metabolomic biomarkers over time. We aimed to identify urinary metabolomic biomarkers of diet and assess their reproducibility over time. We conducted a metabolomics analysis among 648 racially/ethnically diverse men and women in the Diet Assessment Sub-study of the Cancer Prevention Study-3 cohort to examine the correlation between >100 food groups/items [101 by a food frequency questionnaire (FFQ), and 105 by repeated 24 h diet recalls (24HRs)] and 1391 metabolites measured in 24 h urine sample replicates, six months apart. Diet–metabolite associations were examined by Pearson’s partial correlation analysis. Biomarkers were evaluated for prediction accuracy assessed using area under the curve (AUC) calculated from the receiver operating characteristic curve and for reproducibility assessed using intraclass correlation coefficients (ICCs). A total of 1708 diet–metabolite associations were identified after Bonferroni correction for multiple comparisons and restricting correlation coefficients to >0.2 or <−0.2 (1570 associations using the FFQ and 933 using 24HRs), 513 unique metabolites correlated with 79 food groups/items. The median ICCs of the 513 putative biomarkers was 0.53 (interquartile range 0.42–0.62). In this study, with comprehensive dietary data and repeated 24 h urinary metabolic profiles, we identified a large number of diet–metabolite correlations and replicated many found in previous studies. Our findings revealed the promise of urine samples for dietary biomarker discovery in a large cohort study and provide important information on biomarker reproducibility, which could facilitate their utilization in future clinical and epidemiological studies.

Untargeted global metabolomic profiling of healthy dogs grouped on the basis of grain inclusivity of their diet and of dogs with subclinical cardiac abnormalities that underwent a diet change

“…15 This unnamed compound was also present in GI diets but to a lesser degree. A study 18,19 in people identified X-25419 in blood and urine to be associated with fish and olive oil ingestion, and a study 20 of dogs with mitral valve disease found that X-25419 was significantly different between healthy dogs predisposed to heart disease and dogs with mild heart disease. Fish is a common protein source for many types of dog diets, but diet was not reported in the dog study.…”

“…Fish is a common protein source for many types of dog diets, but diet was not reported in the dog study. 18 Until structural elucidation is performed, speculation about the clinical importance of X-25419 is not possible.…”

“…A strength of the present study was the absence of advanced cardiac disease, which can change the metabolome. 18 However, it is important to recognize that this methodology is only a biochemical snapshot in time. There are several limitations that should be considered for study interpretation.…”

Food-Derived Uremic Toxins in Chronic Kidney Disease

“…2-methoxyresorcinol is a polyphenol that derives from the consumption of green and black tea [ 33 , 135 ]. Urinary 2-methoxyresorcinol was identified as a biomarker of tea consumption [ 33 ].…”

“…2-methoxyresorcinol is a polyphenol that derives from the consumption of green and black tea [ 33 , 135 ]. Urinary 2-methoxyresorcinol was identified as a biomarker of tea consumption [ 33 ]. However, no studies have been carried out to elucidate its bioavailability and contribution to plasma retention in humans.…”