Effects of wine and Its microbial-derived metabolites on intestinal permeability using simulated gastrointestinal digestion/colonic fermentation and Caco-2 intestinal cell models

This article belongs to the Special Issue Gastrointestinal Microbiota and Gut Barrier Impact Human Health and Disease.This paper explores the effects of wine polyphenols on intestinal permeability in in vitro conditions. A red wine (2500 mg/L of gallic acid equivalents) was sequentially subjected to gastrointestinal and colonic digestion in the Dynamic Gastrointestinal Simulator (simgi®) to obtain two simulated fluids: intestinal-digested wine (IDW) and colonic-digested wine (CDW). The two fluids were incubated with Caco-2 cell monolayers grown in Transwell® inserts, and paracellular permeability was measured as transport of FITC-dextran. Non-significant decreases (p > 0.05) in paracellular permeability were found, which was attributed to the relatively low phenolic concentration in the solutions tested (15.6 and 7.8 mg of gallic acid equivalents/L for IDW and CDW, respectively) as quercetin (200 µM) and one of its microbial-derived phenolic metabolites, 3,4-dihydroxyphenylacetic acid (200 µM), led to significant decreases (p 0.05), was observed. Analysis of the microbiome and microbial activity during wine colonic fermentation revealed relevant changes in the relative abundance of some families/genera (i.e., reduction in Bacteroides and an increase in Veillonella, Escherichia/Shigella and Akkermansia) as well as in the microbial production of SCFA (i.e., a significant increase in propionic acid in the presence of IDW), all of which might affect paracellular permeability. Both direct and indirect (microbiota-mediated) mechanisms might be involved in the protective effects of (wine) polyphenols on intestinal barrier integrity. Overall, this paper reinforces (wine) polyphenols as a promising dietary strategy to improve gut functionality, although further studies are needed to evaluate the effect on the intestinal barrier under different conditions.This research was funded by the Spanish Ministry of Science and Innovation (Spain) (grants AGL2015-64522-C2-1-R and PID2019-108851RB-C21) and the Community of Madrid (ALIBIRD-CM 2020 P2018/BAA-4343). I.Z-P is grateful for the BES-2016-077980 contract.Peer reviewe