{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T20:27:12Z","timestamp":1773692832214,"version":"3.50.1"},"reference-count":107,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T00:00:00Z","timestamp":1678320000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Vet. Sci."],"abstract":"<jats:p>Pharmacological doses of zinc oxide (ZnO) have been widely used in pig industry to control post-weaning diarrhea (PWD) symptoms exacerbated by enterotoxigenic <jats:italic>Escherichia coli<\/jats:italic> F4 infections. Because of environmental issues and regulatory restrictions, ZnO is no longer sustainable, and novel nutritional alternatives to manage PWD are urgently required. Botanicals represent a wide class of compounds employed in animal nutrition because of their diverse beneficial functions. The aim of this study was to investigate the <jats:italic>in vitro<\/jats:italic> protective action of a panel of essential oils and natural extracts on intestinal Caco-2 cells against an <jats:italic>E. coli<\/jats:italic> F4 infection. Moreover, we explored the potential mechanisms of action of all the botanicals compared to ZnO. Amongst the others, thyme essential oil, grape seed extract, and <jats:italic>Capsicum<\/jats:italic> oleoresin were the most effective in maintaining epithelial integrity and reducing bacterial translocation. Their mechanism of action was related to the modulation of cellular inflammatory response, the protection of tight junctions' expression and function, and the control of bacterial virulence, thus resembling the positive functions of ZnO. Moreover, despite their mild effects on the host side, ginger and tea tree essential oils provided promising results in the control of pathogen adhesion when employed during the challenge. These outcomes support the advantages of employing selected botanicals to manage <jats:italic>E. coli<\/jats:italic> F4 infections <jats:italic>in vitro<\/jats:italic>, therefore offering novel environmentally-friendly alternatives to pharmacological doses of ZnO capable to modulate host-pathogen interaction at different levels during PWD in pigs.<\/jats:p>","DOI":"10.3389\/fvets.2023.1141561","type":"journal-article","created":{"date-parts":[[2023,3,9]],"date-time":"2023-03-09T05:29:47Z","timestamp":1678339787000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Botanicals as a zinc oxide alternative to protect intestinal cells from an Escherichia coli F4 infection in vitro by modulation of enterocyte inflammatory response and bacterial virulence"],"prefix":"10.3389","volume":"10","author":[{"given":"Andrea","family":"Bonetti","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Piva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ester","family":"Grilli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ani11030642","article-title":"Towards zero zinc oxide: feeding strategies to manage post-weaning diarrhea in piglets","volume":"11","author":"Bonetti","year":"2021","journal-title":"Animals."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s40813-017-0063-4","article-title":"Swine enteric colibacillosis: diagnosis, therapy and antimicrobial resistance","volume":"3","author":"Luppi","year":"2017","journal-title":"Porcine Health Manag."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/ecosalplus.ESP-0006-2016","article-title":"Animal enterotoxigenic Escherichia coli","volume":"7","author":"Dubreuil","year":"2016","journal-title":"EcoSal Plus"},{"key":"B4","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.vetmic.2009.08.020","article-title":"Disruption of transepithelial resistance by enterotoxigenic Escherichia coli","volume":"141","author":"Johnson","year":"2010","journal-title":"Vet Microbiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"8192","DOI":"10.1155\/2017\/2748192","article-title":"Altered cytokine expression and barrier properties after in vitro infection of porcine epithelial cells with enterotoxigenic Escherichia coli and probiotic Enterococcus faecium","volume":"2017","author":"Kern","year":"2017","journal-title":"Mediators Inflamm"},{"key":"B6","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1111\/j.1365-2672.2010.04889.x","article-title":"Induction of cytokine formation by human intestinal bacteria in gut epithelial cell lines","volume":"110","author":"Bahrami","year":"2011","journal-title":"J Appl Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.micpath.2017.10.037","article-title":"Enterotoxigenic Escherichia coli targeting intestinal epithelial tight junctions: an effective way to alter the barrier integrity","volume":"113","author":"Dubreuil","year":"2017","journal-title":"Microb Pathog."},{"key":"B8","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/j.colsurfa.2014.05.057","article-title":"The contribution of zinc ions to the antimicrobial activity of zinc oxide","volume":"457","author":"Pasquet","year":"2014","journal-title":"Colloids Surf A Physicochem Eng Asp."},{"key":"B9","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3109\/02844319009041278","article-title":"Antibacterial effect of zinc oxide in vitro","volume":"24","author":"S\u00f6derberg","year":"1990","journal-title":"Scand J Plast Reconstr Surg Hand Surg."},{"key":"B10","doi-asserted-by":"publisher","first-page":"38","DOI":"10.5923\/j.health.20120204.04","article-title":"In vitro antibacterial activity and minimum inhibitory concentration of zinc oxide and nano-particle zinc oxide against pathogenic strains","volume":"2","author":"Yousef","year":"2012","journal-title":"Int J Health Sci."},{"key":"B11","first-page":"513","article-title":"Effects of zinc oxide on postweaning diarrhea control in pigs experimentally infected with E.","volume":"50","author":"Mores","year":"1998","journal-title":"coli. 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