Gastrointestinal Digestion of a Grape Pomace Extract: Impact on Intestinal Barrier Permeability and Interaction with Gut Microbiome

Abstract

Grape pomace (GP) is a winemaking by-product rich in polyphenols and fibre. Supplementation with GP extracts has shown potential benefits against oxidative stress- and inflammation-related pathologies. As a new nutritional target, this paper explores the impact of the ingestion of a grape pomace extract on intestinal barrier functionality. A GP extract was sequentially subjected to gastrointestinal and colonic digestion using the dynamic gastrointestinal simulator (simgi®). This generated two simulated fluids: intestinal-digested extract (IDE) and colonic-digested extract (CDE). The effects of these two fluids on paracellular permeability and the expression of tight junction (TJ) proteins (i.e., zonula occludens-1 (ZO-1) and occludin) were assessed in Caco-2-cell monolayers grown in Transwell® inserts. The IDE fluid significantly (p < 0.001) reduced the paracellular transport of FITC-dextran with respect to the control, whereas no significant differences (p > 0.05) were found for CDE, which could be due, at least partially, to the pro-leaky effect of the colonic digestion medium. Accordant slight increases in the mRNA levels of both ZO-1 and occludin were observed for IDE, but without statistical significance. Additionally, the colonic fermentation of the GP extract promoted the production of short-chain fatty acids (SCFA) and phenolic metabolites and led to changes in the relative abundance of some bacteria that might affect paracellular permeability. Overall, this paper reports first trends about the effects of grape pomace extracts on intestinal permeability that would require further confirmation in future experiments.

Bioaccessibility of phenolic compounds using the standardized INFOGEST protocol: A narrative review

“…Phenolic metabolites can also be considered novel compounds, since they may be different from the parent compounds. In general, low‐molecular‐weight molecules can be absorbed in the small intestine, exerting other systemic effects than their precursor phenolic (da Fuentes et al., 2021; Quatrin et al., 2020; Silva et al., 2019; Taladrid et al., 2021).…”

Grape Pomace as a Cardiometabolic Health-Promoting Ingredient: Activity in the Intestinal Environment

“…These studies have demonstrated that grape-derived compounds can counteract permeabilization by studying paracellular flux (e.g., fluoroisothiocyanate-dextran (FITC-dextran)) or transepithelial electrical resistance (TEER) [ 93 , 94 , 95 , 96 ]. In our most recent research, we observed a decrease in paracellular transport of FITC-dextran after incubating Caco-2 monolayers with different GP-digested samples [ 97 ]. We also noted that GP-digested samples resulted in increased production of SCFAs and phenolic acids during colonic fermentation compared to control samples.…”

“…We also noted that GP-digested samples resulted in increased production of SCFAs and phenolic acids during colonic fermentation compared to control samples. This increase in SCFA and phenolic acid production may partially explain the observed decrease in permeabilization [ 97 ]. The mechanisms underlying the enhancement of the gut barrier exerted by GP are varied, including the upregulation of key genes encoding for diverse TJ proteins, such as occludins [ 83 ], claudins [ 83 , 85 ], ZO-1 [ 83 , 89 ], and TJ protein 1 [ 90 ].…”

“…LPS: lipopolysaccharide; ZO: Zonula occludens or tight junction protein. Numbers represent those activities associated with GP in several in vitro and in vivo models: (1) : Pistol et al [ 83 ]; Gil-Cardoso et al [ 89 ]; (2) : Pistol et al [ 83 ]; (3) : Maurer et al [ 85 ]; Pistol et al [ 83 ]; (4) : Nallathambi et al [ 90 ]; Reiche and Huber [ 91 ]; (5) : Hidalgo-Liberona et al [ 92 ]; Yang et al [ 93 ]; Cremonini et al [ 94 ]; Gil-Cardonso et al [ 95 ]; González-Quilen et al [ 96 ]; (6) : Taladrid et al [ 97 ].…”

Wild blueberry (V. angustifolium) improves TNFα-induced cell barrier permeability through claudin-1 and oxidative stress modulation in Caco-2 cells

“…On the other side, the authors showed that occludin levels were not modulated by TNF-α, in line with our observations. Taladrid and coworkers 44 found that a PP-rich extract deriving from intestinal digestion of grape pomace was ineffective in modulating mRNA levels of ZO-1 and occludin. Nevertheless, the same extract exerted a reduction of FITC paracellular transport through Caco-2 cell monolayer, indicating how the modulation of IP is determined by complex interactions and several proteins play a decisive role.…”