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Traditionally, acute symptoms have been treated with antibiotics and high doses of zinc oxide (ZnO). However, concerns have been raised regarding the potential for microbial resistance and ecological detriment due to the excessive application of this compound. These concerns highlight the urgency of minimizing the use of ZnO and exploring sustainable nutritional solutions. Hydrolysable tannins (HTs), which are known for their role in traditional medicine for acute gastrointestinal issues, have emerged as a promising alternative. This study examined the combined effect of food-grade HTs and subtherapeutic ZnO concentration on relevant biological functions of Caco-2 cells, a widely used model of the intestinal epithelial barrier. We found that, when used together, ZnO and HTs (ZnO\/HTs) enhanced tissue repair and improved epithelial barrier function, normalizing the expression and functional organization of tight junction proteins. Finally, the ZnO\/HTs combination strengthened enterocytes\u2019 defense against oxidative stress induced by inflammation stimuli. In conclusion, combining ZnO and HTs may offer a suitable and practical approach for decreasing ZnO levels in veterinary nutritional applications.<\/jats:p>","DOI":"10.3390\/biom14060666","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T08:45:37Z","timestamp":1717663537000},"page":"666","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Combination of Hydrolysable Tannins and Zinc Oxide on Enterocyte Functionality: In Vitro Insights"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1899-8628","authenticated-orcid":false,"given":"Francesca","family":"Ciaramellano","sequence":"first","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"},{"name":"European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Scipioni","sequence":"additional","affiliation":[{"name":"European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, 00143 Rome, Italy"},{"name":"Department of Biotechnological and Applied Clinical Sciences, University of L\u2019Aquila, Via Vetoio Snc, 67100 L\u2019Aquila, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Bel\u00e0","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2264-0458","authenticated-orcid":false,"given":"Giulia","family":"Pignataro","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giacomo","family":"Giacovazzo","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clotilde Beatrice","family":"Angelucci","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8112-8991","authenticated-orcid":false,"given":"Roberto","family":"Giacominelli-Stuffler","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Gramenzi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6217-698X","authenticated-orcid":false,"given":"Sergio","family":"Oddi","sequence":"additional","affiliation":[{"name":"Department of Veterinary Medicine, University of Teramo, 64100 Teramo, Italy"},{"name":"European Center for Brain Research (CERC), Santa Lucia Foundation IRCCS, 00143 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Buckley, A., and Turner, J.R. 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