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We investigated how nicotine impacted intestinal microbiota composition and barrier function in MASH. Our study revealed significant intestinal microbiota dysbiosis and upregulated hypoxia-inducible factor 1-alpha (HIF-1\u03b1) levels in nicotine-exposed MASH mice. HIF-1\u03b1 knockdown worsened intestinal barrier dysfunction in nicotine-exposed MASH mice. This exacerbation resulted from the suppression of MEK\/ERK signaling pathway phosphorylation in\n                    <jats:italic>HIF-1\u03b1<\/jats:italic>\n                    -deficient mice.\n                    <jats:italic>Lactobacillus rhamnosus<\/jats:italic>\n                    GG supernatant can alleviate hepatic injury in nicotine-exposed MASH mice; however, this protective effect was abolished in the absence of\n                    <jats:italic>HIF-1\u03b1<\/jats:italic>\n                    . Taken together, this study reveals a critical pathologic role of nicotine in exacerbating MASH through intestinal microbiota disruption and barrier dysfunction, which is associated with the downregulation of HIF-1\u03b1 in the intestine. It also suggests exogenous probiotic supplementation as a potential therapeutic strategy for mitigating nicotine-induced MASH progression.\n                  <\/jats:p>","DOI":"10.1038\/s42003-025-09280-5","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T10:03:02Z","timestamp":1764928982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Nicotine exacerbates MASH via inducing intestinal dysbiosis and barrier dysfunction"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0021-823X","authenticated-orcid":false,"given":"Fangfang","family":"Yi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8996-1398","authenticated-orcid":false,"given":"Jinyong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3788-0684","authenticated-orcid":false,"given":"Yi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5835-2396","authenticated-orcid":false,"given":"Yuanhang","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4655-3837","authenticated-orcid":false,"given":"Hongfei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5301-9536","authenticated-orcid":false,"given":"Yilun","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujuan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4165-1691","authenticated-orcid":false,"given":"Sizhe","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaodong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4471-3083","authenticated-orcid":false,"given":"Yongping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8895-8536","authenticated-orcid":false,"given":"Dazhi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"9280_CR1","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/S2468-1253(23)00275-3","volume":"9","author":"JA Thomas","year":"2024","unstructured":"Thomas, J. 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