Exploring the effects of phenolic compounds to reduce intestinal damage and improve the intestinal barrier integrity: A systematic review of in vivo animal studies

complications and disease such as sepsis and death, whereas, the role of food bioactive molecules (i. e. phenolic compounds (PCs) on the intestinal barrier, is still unknown. The current aim was to explore the benefits of the oral PC administration on the intestinal barrier integrity in animals. Methods: The effects of PCs on the intestinal barrier integrity in in vivo animal models of intestinal inflammation were assessed up-to August 2020 from the PubMed, SCOPUS, and Cochrane Library databases under the PRISMA methodology. The risk of bias was assessed from ARRAY and SCYRCLE tools. Results: From 1241 articles, 14 studies were included. In animals, oral resveratrol (n ¿ 6) improves the intestinal barrier integrity and reduces intestinal damage. Additionally, grape seed extract (n ¿ 2), curcumin (n ¿ 1), genistein (n ¿ 1), chlorogenic acid (n ¿ 1), grape pomace (n ¿ 1), olive leaf (n ¿ 1) or cranberry extract (n ¿ 1) improve the intestinal barrier integrity downregulating various inflammatory molecules (TNF-a, and other interleukins), and increasing the antioxidant enzymes in animals. Furthermore, resveratrol, quercetin, epigallocatechin, and other PCs improve the epithelial barrier integrity and pro-inflammatory molecule expression in the intestinal epithelia. Conclusions: The oral PC administration in animals improves the intestinal barrier integrity and function from three main mechanisms: 1) The reduction of pro-inflammatory molecules, 2) the improvement in tight-junction protein expression, and 3) the improvement of the antioxidant intracellular activity suggesting the potential use of PCs in the management of intestinal injury in humans, particularly for resveratrol, the most studied PC.The AppleCOR Project (Subproject AGL2016-76943-C2-2-R and Subproject AGL2016-76943-C2-1-R) has been possible with the support of Ministerio de Economía, Indústria y Competitividad, the Agencia Estatal de Investigación (AEI) and the European Regional Development Fund (ERDF); NFOC-Salut group is a consolidated research group of Generalitat de Catalunya, Spain (2017 SGR 522). S-R. BA. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 713679. This journal article has been possible with the support of the Universitat Rovira i Virgili (URV) and the Fundacio Catalunya-La Pedrera (FCLP) (Reference number: 2017MFP-COFUND-30). Ú-C has a Pla estrategic de recerca i innovacio en salut (PERIS) post-doctoral grant (SLT002/16/00239; Catalunya, Spain) from Generalitat de Catalunya. M.J. Motilva thanks to Consejo Superior de Investigaciones Científicas-CSIC for partial funding through the “Ayudas incorporacion a escalas cien- tíficas CSIC, 2018” (Reference 201870I129)