Polyphenols present in wine may favorably influence human health by means of modifying the metabolic activity and/or composition of gut microbiota. The aim of this study was to evaluate the impact of red wine on colonic metabolism using a novel Dynamic Gastrointestinal Simulator (namely SIMGI), inoculated with human feces of healthy volunteers (n = 2). Main wine phenolic compounds and their metabolites, ammonium and short-chain fatty acids (SCFAs) as well as main microbial groups were monitored in samples from the three colon compartments - ascending, transverse and descending - after feeding the system with red wine (225 mL). Significant increases were found for gallic acid, protocatechuic acid, 3-O-methylgallic acid, 4-hydroxybenzoic acid, 3,4-dihydroxyphenylpropionic acid, vanillic acid, syringic acid and salicylic add after wine feeding. Concurrently, a decrease in ammonium ion and an increase in the proportion of butanoic acid were observed. In turn, the microbiota metabolic activity was found different between the two individuals and among the three compartments, with the main changes occurring in the ascending colon. These results highlight that red wine modulates the metabolic activity of colonic microbiota in vitro, which could be physiologically relevant, and contribute to our understanding on the complex metabolic fate of dietary polyphenols and polyphenols-microbiota interactions. (C) 2015 Elsevier Ltd. All rights reserved.