{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T16:16:58Z","timestamp":1788970618472,"version":"build-2803163510"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T00:00:00Z","timestamp":1616630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014857","name":"National Natural Science Foundation of China-Guangdong Joint Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100014857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>This study aimed to investigate the effects of dietary anethole supplementation on the growth performance, intestinal barrier function, inflammatory response, and intestinal microbiota of piglets challenged with enterotoxigenic <jats:italic>Escherichia coli<\/jats:italic> K88. Thirty-six weaned piglets (24 \u00b1 1 days old) were randomly allocated into four treatment groups: (1) sham challenge (CON); (2) <jats:italic>Escherichia coli<\/jats:italic> K88 challenge (ETEC); (3) <jats:italic>Escherichia coli<\/jats:italic> K88 challenge + antibiotics (ATB); and (4) <jats:italic>Escherichia coli<\/jats:italic> K88 challenge + anethole (AN). On day 12, the piglets in the ETEC, ATB, and AN group were challenged with 10 mL <jats:italic>E. coli<\/jats:italic> K88 (5 \u00d7 10<jats:sup>9<\/jats:sup> CFU\/mL), whereas the piglets in the CON group were orally injected with 10 mL nutrient broth. On day 19, all the piglets were euthanized for sample collection. The results showed that the feed conversion ratio (FCR) was increased in the <jats:italic>Escherichia coli<\/jats:italic> K88-challenged piglets, which was reversed by the administration of antibiotics or anethole (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). The duodenum and jejunum of the piglets in ETEC group exhibited greater villous atrophy and intestinal morphology disruption than those of the piglets in CON, ATB, and AN groups (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Administration of anethole protected intestinal barrier function and upregulated mucosal layer (mRNA expression of mucin-1 in the jejunum) and tight junction proteins (protein abundance of ZO-1 and Claudin-1 in the ileum) of the piglets challenged with <jats:italic>Escherichia coli<\/jats:italic> K88 (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). In addition, administration of antibiotics or anethole numerically reduced the plasma concentrations of IL-1\u03b2 and TNF-\u03b1 (<jats:italic>P<\/jats:italic> &amp;lt; 0.1) and decreased the mRNA expression of TLR5, TLR9, MyD88, IL-1\u03b2, TNF-\u03b1, IL-6, and IL-10 in the jejunum of the piglets after challenge with <jats:italic>Escherichia coli<\/jats:italic> K88 (<jats:italic>P<\/jats:italic> &amp;lt; 0.05). Dietary anethole supplementation enriched the abundance of beneficial flora in the intestines of the piglets. In summary, anethole can improve the growth performance of weaned piglets infected by ETEC through attenuating intestinal barrier disruption and intestinal inflammation.<\/jats:p>","DOI":"10.3389\/fmicb.2021.647242","type":"journal-article","created":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T05:50:15Z","timestamp":1616651415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":41,"title":["Anethole Attenuates Enterotoxigenic Escherichia coli-Induced Intestinal Barrier Disruption and Intestinal Inflammation via Modification of TLR Signaling and Intestinal Microbiota"],"prefix":"10.3389","volume":"12","author":[{"given":"Qingyuan","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanzhen","family":"Qiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shihai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wutai","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,3,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.2353\/ajpath.2010.100371","article-title":"IL-1\u03b2-induced increase in intestinal epithelial tight junction permeability is mediated by MEKK-1 activation of canonical NF-\u03baB pathway.","volume":"177","author":"Al-Sadi","year":"2010","journal-title":"Am. J. Pathol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1016\/j.fitote.2010.11.003","article-title":"Anticholinesterase activity of standardized extract of Illicium verum Hook. f. fruits.","volume":"82","author":"Bhadra","year":"2011","journal-title":"Fitoterapia"},{"key":"B3","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1128\/am.9.2.175-180.1961","article-title":"A Study of bacterial species from the rumen which produce ammonia from protein hydrolysate.","volume":"9","author":"Bladen","year":"1961","journal-title":"Appl. Microbiol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1038\/35014038","article-title":"Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor.","volume":"2","author":"Burns","year":"2000","journal-title":"Nat. Cell Biol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1136\/gut.2004.062794","article-title":"Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2.","volume":"54","author":"Cario","year":"2005","journal-title":"Gut"},{"key":"B6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.15232\/pas.2015-01433","article-title":"Effect of anise oil fed to lactating sows and nursery pigs on sow feed intake, piglet performance, and weanling pig feed intake and growth performance.","volume":"32","author":"Charal","year":"2016","journal-title":"Prof. Anim Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"949","DOI":"10.1017\/S0007114517003051","article-title":"Effects of dietary live yeast supplementation on growth performance, diarrhoea severity, intestinal permeability and immunological parameters of weaned piglets challenged with enterotoxigenic Escherichia Coli K88.","volume":"118","author":"Che","year":"2017","journal-title":"Br. J. Nutr."},{"key":"B8","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1155\/2012\/756284","article-title":"The whole shebang: The gastrointestinal tract, Escherichia coli enterotoxins and secretion.","volume":"14","author":"Dubreuil","year":"2012","journal-title":"Curr. Issues Mol. Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1079\/AHR2005105","article-title":"Escherichia coli in postweaning diarrhea in pigs: an update on bacterial types, pathogenesis, and prevention strategies.","volume":"6","author":"Fairbrother","year":"2005","journal-title":"Anim. Health Res. Rev"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094891","article-title":"Lactobacillus amylovorus inhibits the TLR4 inflammatory signaling triggered by enterotoxigenic Escherichia coli via modulation of the negative regulators and involvement of TLR2 in intestinal Caco-2 cells and pig explants.","volume":"9","author":"Finamore","year":"2014","journal-title":"PLoS One"},{"key":"B11","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1016\/j.micinf.2009.10.002","article-title":"Molecular mechanisms of enterotoxigenic Escherichia coli infection.","volume":"12","author":"Fleckenstein","year":"2010","journal-title":"Microbes Infect."},{"key":"B12","doi-asserted-by":"publisher","first-page":"5614","DOI":"10.2527\/jas.2013-6528","article-title":"Changes in gut microbial populations, intestinal morphology, expression of tight junction proteins, and cytokine production between two pig breeds after challenge with Escherichia coli K88: A comparative study.","volume":"91","author":"Gao","year":"2013","journal-title":"J. Anim. Sci."},{"key":"B13","doi-asserted-by":"publisher","first-page":"20547","DOI":"10.1074\/jbc.M110.121319","article-title":"Muc1 cell surface mucin attenuates epithelial inflammation in response to a common mucosal pathogen.","volume":"285","author":"Guang","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B14","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1016\/j.molmed.2007.09.002","article-title":"Signaling to NF-\u03baB by Toll-like receptors.","volume":"13","author":"Kawai","year":"2007","journal-title":"Trends Mol Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"2625","DOI":"10.3382\/ps.2013-03092","article-title":"Immune effects of dietary anethole on Eimeria acervulina infection.","volume":"92","author":"Kim","year":"2013","journal-title":"Poult. Sci."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1038\/srep12018","article-title":"A novel crosstalk between TLR4- and NOD2- mediated signaling in the regulation of intestinal inflammation.","volume":"5","author":"Kim","year":"2015","journal-title":"Sci. Rep."},{"key":"B17","doi-asserted-by":"publisher","first-page":"11","DOI":"10.5217\/ir.2015.13.1.11","article-title":"Intestinal permeability regulation by tight junction: Implication on inflammatory bowel diseases.","volume":"13","author":"Lee","year":"2015","journal-title":"Intest. Res"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0040666","article-title":"Risks associated with high-dose Lactobacillus rhamnosus in an Escherichia coli model of piglet diarrhea: Intestinal microbiota and immune imbalances.","volume":"7","author":"Li","year":"2012","journal-title":"PLoS One."},{"key":"B19","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method.","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.cyto.2008.01.006","article-title":"LPS\/TLR4 signal transduction pathway.","volume":"42","author":"Lu","year":"2008","journal-title":"Cytokine"},{"key":"B21","doi-asserted-by":"publisher","first-page":"G367","DOI":"10.1152\/ajpgi.00173.2003","article-title":"TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation.","volume":"286","author":"Ma","year":"2004","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/jps.3030480616","article-title":"Antimicrobial substances from seeds.","volume":"48","author":"Maruzzella","year":"2010","journal-title":"J. Am. Pharm. Assoc"},{"key":"B23","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1136\/gut.44.2.283","article-title":"Cytokine regulation of epithelial permeability and ion transport.","volume":"44","author":"McKay","year":"1999","journal-title":"Gut"},{"key":"B24","doi-asserted-by":"publisher","first-page":"92","DOI":"10.2527\/jas.2008-1381","article-title":"Dietary plasma proteins, the intestinal immune system, and the barrier functions of the intestinal mucosa.","volume":"87","author":"Moret\u00f3","year":"2009","journal-title":"J"},{"key":"B25","year":"2012","journal-title":"Nutrient Requirements of Swine"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/1829632","article-title":"Protective effects of benzoic acid, Bacillus coagulans, and oregano oil on intestinal injury caused by enterotoxigenic Escherichia coli in weaned piglets.","volume":"2018","author":"Pu","year":"2018","journal-title":"Biomed. Res. Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"278","DOI":"10.1038\/ajg.2014.427","article-title":"Intestinal microbiota and diet in IBS: causes, consequences, or epiphenomena?","volume":"110","author":"Rajili\u0107-Stojanovi\u0107","year":"2015","journal-title":"Am. J. Gastroenterol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2019\/6416187","article-title":"Immune response of piglets receiving mixture of formic and propionic acid alone or with either capric acid or Bacillus Licheniformis after Escherichia coli challenge.","volume":"2019","author":"Ren","year":"2019","journal-title":"Biomed. Res. Int."},{"key":"B29","doi-asserted-by":"publisher","first-page":"3205","DOI":"10.1099\/mic.0.043257-0","article-title":"Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives.","volume":"156","author":"Salonen","year":"2010","journal-title":"Microbiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1111\/jpn.12684","article-title":"Relationships between body temperatures and inflammation indicators under physiological and pathophysiological conditions in pigs exposed to systemic lipopolysaccharide and dietary deoxynivalenol.","volume":"102","author":"Tesch","year":"2018","journal-title":"J. Anim. Physiol. Anim. Nutr."},{"key":"B31","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1038\/nri2653","article-title":"Intestinal mucosal barrier function in health and disease.","volume":"9","author":"Turner","year":"2009","journal-title":"Nat. Rev. Immunol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1038\/ni968","article-title":"SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling.","volume":"4","author":"Wald","year":"2003","journal-title":"Nat. Immunol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"140","DOI":"10.2527\/jas.2007-0459","article-title":"Use of phytogenic products as feed additives for swine and poultry.","volume":"86","author":"Windisch","year":"2008","journal-title":"J. Anim. Sci."},{"key":"B34","doi-asserted-by":"publisher","first-page":"634","DOI":"10.2527\/2005.833634x","article-title":"Effect of glutamine and spray-dried plasma on growth performance, small intestinal morphology, and immune responses of Escherichia coli K88+-challenged weaned pigs.","volume":"83","author":"Yi","year":"2005","journal-title":"J. Anim. Sci."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1072","DOI":"10.1021\/acs.est.6b06424","article-title":"China must reduce its antibiotic use.","volume":"51","author":"Ying","year":"2017","journal-title":"Environ. Sci. Technol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"998","DOI":"10.1007\/BF01711080","article-title":"Passive protective effect of chicken egg yolk immunoglobulins against experimental enterotoxigenic Escherichia coli infection in neonatal piglets.","volume":"60","author":"Yokoyama","year":"1992","journal-title":"Infect. Immun."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-015-0004-5","article-title":"Essential oil and aromatic plants as feed additives in non-ruminant nutrition: a review.","volume":"6","author":"Zeng","year":"2015","journal-title":"J Anim Sci Biotechnol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1623","DOI":"10.1007\/s00284-011-9906-4","article-title":"Modulatory effects of Lactobacillus salivarius on intestinal mucosal immunity of piglets.","volume":"62","author":"Zhang","year":"2011","journal-title":"Curr. Microbiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1017\/S0007114518001101","article-title":"Ethanolamine enhances intestinal functions by altering gut microbiome and mucosal anti-stress capacity in weaned rats.","volume":"120","author":"Zhou","year":"2018","journal-title":"Br. J. Nutr."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.647242\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,3,25]],"date-time":"2021-03-25T05:50:18Z","timestamp":1616651418000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2021.647242\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,25]]},"references-count":39,"alternative-id":["10.3389\/fmicb.2021.647242"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2021.647242","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,25]]},"article-number":"647242"}}