Nutrimetabolomics fingerprinting to identify biomarkers of bread exposure in a free-living population from the PREDIMED study cohort

Abstract

Bread is one of the most widely consumed foods. Its impact on human health is currently of special interest for researchers. We aimed to identify biomarkers of bread consumption by applying a nutrimetabolomic approach to a free-living population. An untargeted HPLC-q-TOF-MS and multivariate analysis was applied to human urine from 155 subjects stratified by habitual bread consumption in three groups: non-consumers of bread (NCB, n=56), white-bread consumers (WHB, n=48) and whole-grain bread consumers (WGB, n=51). The most differential metabolites (VIP ≥1.5) included compounds originating from cereal plant phytochemicals such as benzoxazinoids and alkylresorcinol metabolites, and compounds produced by gut microbiota (such as enterolactones, hydroxybenzoic and dihydroferulic acid metabolites). Pyrraline, riboflavin, 3-indolecarboxylic acid glucuronide, 2,8-dihydroxyquinoline glucuronide and N-α-acetylcitrulline were also tentatively identified. In order to combine multiple metabolites 2 in a model to predict bread consumption, a stepwise logistic regression analysis was used.Receiver operating curves were constructed to evaluate the global performance of individual metabolites and their combination. The area under the curve values [AUC (95% CI)] of combined models ranged from 77.8% (69.1%-86.4%) to 93.7% (89.4%-98.1%), whereas the AUC for the metabolites included in the models had weak values when they were evaluated individually: from 58.1 % (46.6-69.7 %) to 78.4% (69.8%-87.1%). Our study showed that a daily bread intake significantly impacted on the urinary metabolome, despite being examined under uncontrolled free-living conditions. We further concluded that a combination of several biomarkers of exposure is better than a single biomarker for the predictive ability of discriminative analysis.

Urinary Biomarkers of Whole Grain Wheat Intake Identified by Non-targeted and Targeted Metabolomics Approaches

“…8b), despite the reports that glycine conjugated and unconjugated bile acids may be responsible for the discrimination between venous and arterial plasma samples after WG wheat intake in pigs49. Similarly, the lignan metabolite, enterolactone glucuronide ( 26 ), has been reported as a biomarker to distinguish WG rye consumption from RG group39. However, our data showed that the urinary excretion of enterolactone glucuronide in the WG group is not significantly different from the RG group (Table 2 and Fig.…”

“…1) were attributed to wheat phytochemicals ARs and BXs3839. Other altered compounds linked to WG consumption are phenolic acids and related metabolites, such as ferulic acid (FA) sulfate, 1,2,3-benzenetriol sulfates degraded from gallic acid40, 3-methoxycatechol sulfate derived probably from 3-methylgallic acid40, 3-methylcatechol41, and 4-acetylphenol42 (Table 1 and Supplementary Fig.…”

“…However, all of the previous metabolomics studies on WG wheat/rye investigate biomarkers of dietary exposure using merely single spot or 24-h samples3978. This is the first study to identify the appropriate biomarkers as a panel to estimate WG wheat consumption using kinetics parameters.…”

An NMR metabolomics approach reveals a combined-biomarkers model in a wine interventional trial with validation in free-living individuals of the PREDIMED study

“…Altogether, these findings demonstrate that there are several results on combining biomarkers in a model, although it is important to find the simplest combination of metabolites that can produce a proper effective outcome (Xia et al, 2013). The development of robust food biomarkers has important goals aimed at providing better classification of individuals in terms of dietary exposure (Garcia-Aloy et al, 2014), and in turn this would improve assessment of the relationship between diet and chronic disease (O'Gorman et al, 2013).…”

Benzoxazinoids: Cereal phytochemicals with putative therapeutic and health‐protecting properties

“…Upon intake, these compounds were subject to different transformations, primarily N ‐dehydroxylation, deglycosylation, glucuronidation, and sulfation, in addition to direct absorption and transformation into hydroxylated phenylacetamide derivatives and AP sulfate . Recent metabolomic analysis of urine of a very large clinical study in free‐living men and women found various BX‐derived compounds as a biomarker of habitual bread consumption even in the group with habitual white‐bread consumptions . This indicated that bread consumers around the globe are exposed to BXs to a certain degree even if they do not consume rye or wholegrain wheat, which are known to contain high amounts of BXs.…”