{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:16:03Z","timestamp":1791231363483,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,4,18]],"date-time":"2025-04-18T00:00:00Z","timestamp":1744934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32372897"],"award-info":[{"award-number":["32372897"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["SCCXTD-2024-8"],"award-info":[{"award-number":["SCCXTD-2024-8"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Innovation Team of Sichuan Province","award":["32372897"],"award-info":[{"award-number":["32372897"]}]},{"name":"Innovation Team of Sichuan Province","award":["SCCXTD-2024-8"],"award-info":[{"award-number":["SCCXTD-2024-8"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Sialyllactose (SL), a bioactive trisaccharide abundant in porcine colostrum, demonstrates multifunctional properties including antimicrobial activity, immune regulation, and apoptosis inhibition. This research uncovers the mechanisms by which SL mitigates enterotoxigenic Escherichia coli (ETEC)-mediated damage to intestinal barrier integrity, employing IPEC-J2 porcine epithelial models. SL pre-treatment effectively blocked pathogen adhesion by competitively binding to cellular receptors, concurrently mitigating inflammation through significant suppression of TNF-\u03b1, IL-1\u03b2, and IL-6 expression (p &lt; 0.05). Notably, SL exhibited functional parallels to the NF-\u03baB inhibitor BAY11-7082, jointly enhancing tight junction integrity via ZO-1 protein stabilization and inhibiting pro-inflammatory signaling through coordinated suppression of I\u03baB-\u03b1\/NF-\u03baB phosphorylation cascades. The dual-action mechanism combines molecular interception of microbial attachment with intracellular modulation of the TLR4\/MyD88\/NF-\u03baB pathway, effectively resolving both pathogenic colonization and inflammatory amplification. These findings position SL as a potential therapeutic application nutraceutical for livestock, with the capacity to address post-weaning porcine enteritis through functional feed formulations that synergistically enhance intestinal barrier resilience while curbing ETEC-mediated inflammatory pathogenesis.<\/jats:p>","DOI":"10.3390\/ijms26083860","type":"journal-article","created":{"date-parts":[[2025,4,20]],"date-time":"2025-04-20T20:24:16Z","timestamp":1745180656000},"page":"3860","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sialyllactose Attenuates Inflammation and Injury of Intestinal Epithelial Cells upon Enterotoxigenic Escherichia coli Infection"],"prefix":"10.3390","volume":"26","author":[{"given":"Qiming","family":"Duan","sequence":"first","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6605-6742","authenticated-orcid":false,"given":"Bing","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5092-9297","authenticated-orcid":false,"given":"Zhiqing","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuheng","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zheng","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6292-7747","authenticated-orcid":false,"given":"Xiangbing","family":"Mao","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8486-1611","authenticated-orcid":false,"given":"Jie","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junqiu","family":"Luo","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7476-3914","authenticated-orcid":false,"given":"Hui","family":"Yan","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1963-9766","authenticated-orcid":false,"given":"Jun","family":"He","sequence":"additional","affiliation":[{"name":"Institute of Animal Nutrition, Sichuan Agricultural University, Chengdu 611130, China"},{"name":"Key Laboratory for Animal Disease-Resistance Nutrition, Chengdu 611130, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1016\/j.vaccine.2014.11.049","article-title":"An assessment of enterotoxigenic Escherichia coli and Shigella vaccine candidates for infants and children","volume":"33","author":"Walker","year":"2015","journal-title":"Vaccine"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1128\/ecosalplus.esp-0006-2016","article-title":"Animal Enterotoxigenic Escherichia coli","volume":"7","author":"Dubreuil","year":"2016","journal-title":"EcoSal Plus"},{"key":"ref_4","doi-asserted-by":"crossref","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":"ref_5","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1186\/s40813-016-0039-9","article-title":"Prevalence of virulence factors in enterotoxigenic Escherichia coli isolated from pigs with post-weaning diarrhoea in Europe","volume":"2","author":"Luppi","year":"2016","journal-title":"Porc. Health Manag."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e13118","DOI":"10.1111\/nmo.13118","article-title":"Early weaning stress induces chronic functional diarrhea, intestinal barrier defects, and increased mast cell activity in a porcine model of early life adversity","volume":"29","author":"Pohl","year":"2017","journal-title":"Neurogastroenterol. Motil."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2186115","DOI":"10.1080\/19490976.2023.2186115","article-title":"Functional effects of human milk oligosaccharides (HMOs)","volume":"15","author":"Dinleyici","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wici\u0144ski, M., Sawicka, E., G\u0119balski, J., Kubiak, K., and Malinowski, B. (2020). Human Milk Oligosaccharides: Health Benefits, Potential Applications in Infant Formulas, and Pharmacology. Nutrients, 12.","DOI":"10.3390\/nu12010266"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"118738","DOI":"10.1016\/j.carbpol.2021.118738","article-title":"Human milk oligosaccharides and infant gut microbiota: Molecular structures, utilization strategies and immune function","volume":"276","author":"Zhang","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.earlhumdev.2015.09.001","article-title":"The functional biology of human milk oligosaccharides","volume":"91","author":"Bode","year":"2015","journal-title":"Early Hum. Dev."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Zhang, J., Zhang, W., and Mu, W. (2023). Recent progress on health effects and biosynthesis of two key sialylated human milk oligosaccharides, 3\u2019-sialyllactose and 6\u2019-sialyllactose. Biotechnol. Adv., 62.","DOI":"10.1016\/j.biotechadv.2022.108058"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2727","DOI":"10.1016\/j.foodchem.2013.05.040","article-title":"Adhesion of enterotoxigenic Escherichia coli strains to neoglycans synthesised with prebiotic galactooligosaccharides","volume":"141","year":"2013","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/pr.2015.262","article-title":"Human milk glycosaminoglycans inhibit in vitro the adhesion of Escherichia coli and Salmonella fyris to human intestinal cells","volume":"79","author":"Coppa","year":"2016","journal-title":"Pediatr. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0168-1702(01)00228-3","article-title":"Comparison of the sialic acid binding activity of transmissible gastroenteritis coronavirus and E. coli K99","volume":"75","author":"Schwegmann","year":"2001","journal-title":"Virus Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1099\/00221287-137-7-1591","article-title":"Adhesion of K99 fimbriated Escherichia coli to pig intestinal epithelium: Correlation of adhesive and non-adhesive phenotypes with the sialoglycolipid content","volume":"137","author":"Seignole","year":"1991","journal-title":"J. Gen. Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1128\/iai.58.1.98-106.1990","article-title":"Glycoprotein glycans that inhibit adhesion of Escherichia coli mediated by K99 fimbriae: Treatment of experimental colibacillosis","volume":"58","author":"Mouricout","year":"1990","journal-title":"Infect. Immun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"118316","DOI":"10.1016\/j.carbpol.2021.118316","article-title":"Alginate oligosaccharide protects against enterotoxigenic Escherichia coli-induced porcine intestinal barrier injury","volume":"270","author":"Wan","year":"2021","journal-title":"Carbohydr. Polym."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1203\/01.pdr.0000200805.45593.17","article-title":"Human milk oligosaccharides inhibit the adhesion to Caco-2 cells of diarrheal pathogens: Escherichia coli, Vibrio cholerae, and Salmonella fyris","volume":"59","author":"Coppa","year":"2006","journal-title":"Pediatr. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1016\/j.ijbiomac.2008.11.009","article-title":"Biorecognition of Escherichia coli K88 adhesin for glycated porcine albumin","volume":"44","year":"2009","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1093\/glycob\/cws074","article-title":"Human milk oligosaccharides: Every baby needs a sugar mama","volume":"22","author":"Bode","year":"2012","journal-title":"Glycobiology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104929","DOI":"10.1016\/j.micinf.2021.104929","article-title":"The prebiotic effect of human milk oligosaccharides 3\u2019- and 6\u2019-sialyllactose on adhesion and biofilm formation by Clostridioides difficile\u2014Pilot study","volume":"24","author":"Piotrowski","year":"2022","journal-title":"Microbes Infect."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2950","DOI":"10.1080\/14767058.2018.1450864","article-title":"Breast milk oligosaccharides: Effects of 2\u2032-fucosyllactose and 6\u2032-sialyllactose on the adhesion of Escherichia coli and Salmonella fyris to Caco-2 cells","volume":"32","author":"Facinelli","year":"2019","journal-title":"J. Matern. Fetal Neonatal Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1007\/s00011-023-01801-4","article-title":"Targeting MyD88: Therapeutic mechanisms and potential applications of the specific inhibitor ST2825","volume":"72","author":"Liu","year":"2023","journal-title":"Inflamm. Res."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Wei, J., Zhang, Y., Li, H., Wang, F., and Yao, S. (2023). Toll-like receptor 4: A potential therapeutic target for multiple human diseases. Biomed. Pharmacother., 166.","DOI":"10.1016\/j.biopha.2023.115338"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1016\/0955-0674(93)90024-K","article-title":"The structure and regulation of tight junctions","volume":"5","author":"Anderson","year":"1993","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Qiao, J., Sun, Z., Liang, D., and Li, H. (2020). Lactobacillus salivarius alleviates inflammation via NF-\u03baB signaling in ETEC K88-induced IPEC-J2 cells. J. Anim. Sci. Biotechnol., 11.","DOI":"10.1186\/s40104-020-00488-5"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/j.carbpol.2019.05.036","article-title":"Chitosan oligosaccharide-mediated attenuation of LPS-induced inflammation in IPEC-J2 cells is related to the TLR4\/NF-\u03baB signaling pathway","volume":"219","author":"Shi","year":"2019","journal-title":"Carbohydr. Polym."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"673847","DOI":"10.1155\/2015\/673847","article-title":"Polymethoxyflavone Apigenin-Trimethylether Suppresses LPS-Induced Inflammatory Response in Nontransformed Porcine Intestinal Cell Line IPEC-J2","volume":"2015","author":"Farkas","year":"2015","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1016\/j.ijbiomac.2019.11.088","article-title":"Hippophae rhamnoides polysaccharides protect IPEC-J2 cells from LPS-induced inflammation, apoptosis and barrier dysfunction in vitro via inhibiting TLR4\/NF-\u03baB signaling pathway","volume":"155","author":"Zhao","year":"2020","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.cell.2010.01.022","article-title":"Pattern recognition receptors and inflammation","volume":"140","author":"Takeuchi","year":"2010","journal-title":"Cell"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Fu, Q., Lin, Q., Chen, D., Yu, B., Luo, Y., Zheng, P., Mao, X., Huang, Z., Yu, J., and Luo, J. (2022). \u03b2-defensin 118 attenuates inflammation and injury of intestinal epithelial cells upon enterotoxigenic Escherichia coli challenge. BMC Vet. Res., 18.","DOI":"10.1186\/s12917-022-03242-3"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41390-020-0852-3","article-title":"The human milk oligosaccharides 2\u2019-fucosyllactose and 6\u2019-sialyllactose protect against the development of necrotizing enterocolitis by inhibiting toll-like receptor 4 signaling","volume":"89","author":"Sodhi","year":"2021","journal-title":"Pediatr. Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Won, S., Sayeed, I., Peterson, B.L., Wali, B., Kahn, J.S., and Stein, D.G. (2015). Vitamin D prevents hypoxia\/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0122821"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"107","DOI":"10.4196\/kjpp.2012.16.2.107","article-title":"3,4,5-Trihydroxycinnamic Acid Inhibits LPS-Induced iNOS Expression by Suppressing NF-\u03baB Activation in BV2 Microglial Cells","volume":"16","author":"Lee","year":"2012","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.1110\/ps.04731004","article-title":"Biophysical characterization of the free IkappaBalpha ankyrin repeat domain in solution","volume":"13","author":"Croy","year":"2004","journal-title":"Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lawrence, T. (2009). The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb. Perspect. Biol., 1.","DOI":"10.1101\/cshperspect.a001651"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16908","DOI":"10.3390\/molecules200916908","article-title":"Glossogyne tenuifolia Extract Inhibits TNF-\u03b1-Induced Expression of Adhesion Molecules in Human Umbilical Vein Endothelial Cells via Blocking the NF-kB Signaling Pathway","volume":"20","author":"Hsuan","year":"2015","journal-title":"Molecules"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Duan, Q., Chen, D., Yu, B., Huang, Z., Luo, Y., Zheng, P., Mao, X., Yu, J., Luo, J., and Yan, H. (2022). Effect of sialyllactose on growth performance and intestinal epithelium functions in weaned pigs challenged by enterotoxigenic Escherichia coli. J. Anim. Sci. Biotechnol., 13.","DOI":"10.1186\/s40104-022-00673-8"},{"key":"ref_39","first-page":"e2873","article-title":"In Vitro assay of bacterial adhesion onto mammalian epithelial cells","volume":"51","author":"Letourneau","year":"2011","journal-title":"J. Vis. Exp."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1007\/s10529-006-9127-2","article-title":"Comparison of relative mRNA quantification models and the impact of RNA integrity in quantitative real-time RT-PCR","volume":"28","author":"Fleige","year":"2006","journal-title":"Biotechnol. Lett."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3860\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:17:35Z","timestamp":1760030255000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/8\/3860"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,18]]},"references-count":40,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["ijms26083860"],"URL":"https:\/\/doi.org\/10.3390\/ijms26083860","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,18]]}}}