Plasma kinetics and microbial biotransformation of grape seed flavanols in rats

• Colonic metabolites analysis by HPLC-MS2 after grape seed flavanol ingestion in rats.
• Grape seed flavanols colonic biotransformation pathway in rat plasma.
• Plasma temporal appearance of grape seed flavanols colonic metabolites in rats.

Flavan-3-ols and their oligomeric forms, proanthocyanidins (PAs), are poorly absorbed in the small intestine and reach the colon where gut bacteria enzymes can hydrolyse them to produce small molecular metabolites, which can reach systemic circulation. However, the microbial metabolism of flavanols has been poorly described in vivo. The aim of this study was to determine the colonic biotransformation pathway and the plasma temporal appearance of grape seed flavanols colonic metabolites in rats. Rat plasma colonic metabolites were analysed by HPLC-MS/MS at 2, 7, 24 and 48 h after 1000 mg/kg of a grape seed PA extract (GSPE) administration. Results indicated that non-metabolised flavanols have peak plasma concentrations 2 h after GSPE administration, whereas the colonic metabolites appeared in plasma later, indicating their gradual colonic biotransformation as valerolactone > phenylpropionic acids ≈ phenylacetic acids > benzoic acids. This study shows how flavanols are biotransformed by gut bacteria in rats over time, facilitating potential bioactive compound identification for particular health effects.