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Nevertheless, the mechanisms predisposing ALD patients to bacterial infections and the role of the NLRP3 inflammasome in the intestinal epithelial barrier in ALD remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established ALD mice models of WT, <jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Gsdmd<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> through chronic alcohol consumption feeding and acute alcohol induction. We compared alterations in gut microbiota, ileitis, and adhesion protein expression, to analyze the role and potential mechanism of NLRP3 in the early onset of ALD. Concurrently, we examined the changes in inflammation and liver damage in the ileum of ALD and healthy mice following foodborne infection with <jats:italic>V. vulnificus<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Compared with the control group, the expression levels of ZO\u20101, Claudin\u20101 and E\u2010cadherin were reduced in the ileum of ALD mice, while those of NLRP3, caspase\u20101(p20), GSDMD\u2010N and IL\u20101\u03b2 were elevated. <jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Gsdmd<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> ALD mice showed an increased gut bacterial load, decreased ileal expression of E\u2010cadherin, more severe ileitis, pronounced liver damage, steatosis and higher plasma levels of FITC\u2010dextran, D\u2010LA and ZO\u20101 compared with WT mice. Notably, <jats:italic>Nlrp3<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> ALD mice exhibited a higher presence of Deferribacterota and Enterobacteriaceae. Furthermore, ALD mice infected with <jats:italic>V. vulnificus<\/jats:italic> infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream infections.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study indicated that NLRP3 activation in the ileum of ALD mice stabilizes the inflammation\u2010related gut microbiota, preserves the intestinal epithelial barrier, and diminishes inflammation and liver injury. Furthermore, the compromised immune defence in ALD mice may contribute to their heightened susceptibility to bacterial pathogens.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Activation of the NLRP3\u2010GSDMD pathway in the ileum of Alcoholic liver disease (ALD) mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NLRP3 activation maintains homeostasis of gut microbiota and intestinal epithelial barrier in ALD mice.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>ALD mice infected with <jats:italic>V. vulnificus<\/jats:italic> infection exhibited no further activation of NLRP3 in the ileum, leading to increased intestinal permeability and bloodstream 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