The Human Metabolism of Nuts Proanthocyanidins does not Reveal Urinary Metabolites Consistent with Distinctive Gut Microbiota Metabotypes

Scope The stratification of individuals according to their gut microbiota metabotypes is crucial to understand the polyphenols health effects as reported for isoflavones and ellagitannins. To date, the existence of human gut microbiota metabotypes associated with proanthocyanidins (PAs) catabolism remains unclear. Methods & Results Sixty-eight healthy volunteers (40 adolescents and 28 adults) consumed a mixture of walnuts, almonds, and hazelnuts for 3 days, providing 163.65 +/- 11.74 mg of PAs. Urine samples were analyzed by ultra-performance LC-ESI-quadrupole time-of-flight. Twenty-one isomers of conjugated valerolactones and valeric acids were identified, which derived from six valerolactone and valeric acid precursors after analysis of hydrolyzed urine. This combined approach allowed discrimination between the inter-individual variability related to phase-II enzymes polymorphisms and the metabolism of PAs by the gut microbiota. No associations of PAs metabolism with gender, age, BMI, or ellagitannin metabotypes were found. Different quantitative excretion was observed after multivariate analysis but not true gut microbiota metabotypes associated with PAs catabolism. Conclusions The metabolism of PAs does not reveal urinary metabolites consistent with distinctive gut microbiota metabotypes. The quantitative excretion of metabolites is inadequate to stratify individuals due to the strong influence of external factors (source, quantity, and time of the last intake of PAs, etc.).