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

Abstract

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.).

Where to Look into the Puzzle of Polyphenols and Health? The Postbiotics and Gut Microbiota Associated with Human Metabotypes

“…As previously shown, there are gut microbial communities involved in the metabolism of polyphenols, such as ellagitannins, isoflavones, proanthocyanidins, lignans, flavanones, proanthocyanidins, and prenylflavonoids (Tables 1 and 2). As in the case of enterotypes, the metabolism of flavanones, [ 146,147 ] lignans, [ 59,148 ] and proanthocyanidins [ 149 ] can also lead to inter‐individual variations by a metabolite production gradient (a continuous variation among individuals). However, no differential human metabotypes are present in the metabolism of these phenolics.…”

“…These flavonoids, especially in the case of oligomeric proanthocyanidins, reach the colon almost intact and are sequentially metabolized by the gut microbiota to yield a cascade of metabolites, that is, phenylvalerolactone derivatives, phenylvaleric acids, phenylpropionic acids, phenylacetic acids, and benzoic acids ( Figure 3 ). [ 149,150,152 ] The final metabolites in this catabolic pathway are not specific to proanthocyanidin catabolism, but they are also common to the gut microbial catabolism of many other polyphenols (flavonoids and non‐flavonoids). [ 153 ] Therefore, the binary response of metabotypes is not accomplished, that is, the presence versus absence of unique metabolites.…”

“…This means that the analysis of intermediates, including phenylvalerolactones, is influenced by many variables such as the source and concentration of proanthocyanidins, the lag period between the last intake of precursor and the sample analysis, the concomitant intake of other food compounds, etc., which lead to misleading results concerning the qualitative and quantitative production of metabolites. [ 149 ]…”

Dietary Phenolics against Breast Cancer. A Critical Evidence-Based Review and Future Perspectives

“…In this regard, a highly variable metabolism between individuals has been described for some phenolic compounds. This allows for grouping the population according to the excretion of the metabolized compound into "high or low producers", as it occurs in the metabolism of the phenolic precursor-derived metabolite pairs hesperidin-hesperetin [147], lignans-enterolignans [148], ellagic acid-urolithins [149] and procyanidins-valerolactones [150,151]. Besides, specific metabotypes, attributed to the different composition and functionality of the gut microbiota, have been described in the case of urolithins [146,152] or isoflavones [153], allowing the stratification of individuals based on the production of specific metabolites associated with a particular gut microbiota ecology.…”

Food Ellagitannins: Structure, Metabolomic Fate, and Biological Properties

“…Ellagitannins, ellagic acid, and their metabolites have been reported to exhibit numerous beneficial effects on human health including anti-inflammatory, anticancer, antioxidant, prebiotic, and cardioprotective properties [21,54]. However, in vitro studies with cells or in vivo studies with animals could give inconsistent or untranslatable information about bioactivity of these metabolites in humans.…”