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Along with the restriction of antibiotics, natural compounds targeting bacterial virulence factors are supposed to be efficacious and attractive alternatives for controlling ETEC infection. This study aimed to investigate the influence of dihydromyricetin (DMY), a natural flavonoid compound, on the expression of virulence factors of ETEC and intestinal inflammatory injury.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>DMY interfered with the quorum sensing (QS) of ETEC K88 since it decreased AI-2 secretion and downregulated the expression of LuxS and Pfs, which dominate AI-2 production, and decreased the expression mRNA level of genes (<jats:italic>lsrA<\/jats:italic>, <jats:italic>lsrB<\/jats:italic>, <jats:italic>lsrC<\/jats:italic>, <jats:italic>lsrD<\/jats:italic>, <jats:italic>lsrK<\/jats:italic>, and <jats:italic>lsrR<\/jats:italic>) that are involved in AI-2 internalization and signal transduction. Additionally, DMY markedly dampened the expression of QS-related virulence genes (<jats:italic>elt-1<\/jats:italic>, <jats:italic>estB<\/jats:italic>, <jats:italic>fliC<\/jats:italic>, <jats:italic>faeG<\/jats:italic>), biofilm formation, cell adhesion, and stress tolerance of ETEC K88. Furthermore, DMY treatment applied to the ETEC K88 infection in mice model resulted in decreased amount of heat-labile (LT) and heat-stable (ST) enterotoxins, reduced production of cAMP and cGMP, downregulated protein level of CFTR and upregulated expression of NHE3 in the ileum. In addition, the mRNA expression of proinflammatory cytokines (TNF-\u03b1, IL-1\u03b2, and IL-6) and histological damage in the ileum were significantly decreased by DMY treatment.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>DMY can inhibit the AI-2 QS and virulence factor expression, thereby attenuating the virulence of ETEC and alleviating intestinal inflammatory damage in ETEC K88-challenged mice. This study indicated that DMY has the potential to be a promising antivirulence agent for combating ETEC infection.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12866-025-03879-8","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T04:04:53Z","timestamp":1744171493000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Dihydromyricetin alleviates ETEC K88-induced intestinal inflammatory injury by inhibiting quorum sensing-related virulence factors"],"prefix":"10.1186","volume":"25","author":[{"given":"Yaqian","family":"Shi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hualin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongyuan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinsheng","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,4,9]]},"reference":[{"key":"3879_CR1","doi-asserted-by":"publisher","first-page":"109117","DOI":"10.1016\/j.vetmic.2021.109117","volume":"258","author":"TJ Laird","year":"2021","unstructured":"Laird TJ, Abraham S, Jordan D, Pluske JR, Hampson DJ, Trott DJ, O\u2019Dea M. 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