Abstract
PurposeExtensive inter-individual variability exists in the production of flavan-3-ol metabolites. Preliminary metabolic phenotypes (metabotypes) have been defined, but there is no consensus on the existence of metabotypes associated with the catabolism of catechins and proanthocyanidins. This study aims at elucidating the presence of different metabotypes in the urinary excretion of main flavan-3-ol colonic metabolites after consumption of cranberry products and at assessing the impact of the statistical technique used for metabotyping.MethodsData on urinary concentrations of phenyl-γ-valerolactones and 3-(hydroxyphenyl)propanoic acid derivatives from two human interventions has been used. Different multivariate statistics, principal component analysis (PCA), cluster analysis, and partial least square-discriminant analysis (PLS-DA), have been considered.ResultsData pre-treatment plays a major role on resulting PCA models. Cluster analysis based on k-means and a final consensus algorithm lead to quantitative-based models, while the expectation–maximization algorithm and clustering according to principal component scores yield metabotypes characterized by quali-quantitative differences in the excretion of colonic metabolites. PLS-DA, together with univariate analyses, has served to validate the urinary metabotypes in the production of flavan-3-ol metabolites and to confirm the robustness of the methodological approach.ConclusionsThis work proposes a methodological workflow for metabotype definition and highlights the importance of data pre-treatment and clustering methods on the final outcomes for a given dataset. It represents an additional step toward the understanding of the inter-individual variability in flavan-3-ol metabolism.Trial registrationThe acute study was registered at clinicaltrials.gov as NCT02517775, August 7, 2015; the chronic study was registered at clinicaltrials.gov as NCT02764749, May 6, 2016.
Highlights
Flavan-3-ols are characteristic polyphenols of tea, cocoa, wine, pome fruits, berries, and nuts, but they are found in stone fruits and legumes [1, 2]
The current work shed light on the existence of metabotypes in the urinary excretion of flavan-3-ol metabolites, which are not characterized by the production/non-production of specific metabolites, but by different quali-quantitative metabolic profiles
Different profiles in the urinary excretion of PLVs and HPPs were observed upon cranberry consumption in two diverse experimental settings, these metabolic profiles being related to specific pathways of phase II metabolism and the type of metabolites produced at colonic level
Summary
Flavan-3-ols are characteristic polyphenols of tea, cocoa, wine, pome fruits (as apple and pear), berries, and nuts, but they are found in stone fruits and legumes [1, 2]. In plant-based foods, they occur as simple monomers or as oligomers and polymers of up to 190 units ( known as proanthocyanidins or condensed tannins) [14] When ingested, both monomeric and high molecular weight flavan-3-ols are poorly absorbed and metabolized in the first gastrointestinal tract, reaching the colon and becoming a suitable substrate for the local microbiota [15]. Conjugated PVLs (sulfate, glucuronide, methoxy, and combinations thereof) are the main colonic circulating metabolites after ingestion of monomeric and polymeric flavan-3-ols by humans [19,20,21,22,23] and, in particular, sulfate and glucuronide derivatives of 5-(3ʹ,4ʹ-dihydroxyphenyl)-γ-valerolactone have been proposed as biomarkers of flavan-3-ol intake [23, 24]. These metabolites may be responsible for the health effects attributed to flavan-3-ols, as they are circulating molecules potentially available to target tissues and organs prior to be excreted in urine [19]
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