{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:28:21Z","timestamp":1792801701509,"version":"4.5.0"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"name":"JSPS KAKENHI","award":["20K16063"],"award-info":[{"award-number":["20K16063"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"DOI":"10.1038\/s41598-025-04680-3","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T03:04:03Z","timestamp":1751425443000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Disruption of small intestinal mucosal homeostasis in mice with amiodarone induced steatohepatitis"],"prefix":"10.1038","volume":"15","author":[{"given":"Shoji","family":"Kawauchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayo","family":"Horibe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoto","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Kunimasa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiyuki","family":"Rikitake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"4680_CR1","first-page":"261","volume":"9","author":"A Grieco","year":"2005","unstructured":"Grieco, A. et al. Fatty liver and drugs. Eur. Rev. Med. Pharmacol. Sci. 9, 261\u2013263 (2005).","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"4680_CR2","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1002\/hep.1840090504","volume":"9","author":"JH Lewis","year":"1989","unstructured":"Lewis, J. H. et al. Amiodarone hepatotoxicity: Prevalence and clinicopathologic correlations among 104 patients. Hepatology 9, 679\u2013685 (1989).","journal-title":"Hepatology"},{"key":"4680_CR3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.cld.2012.05.009","volume":"16","author":"S Larrain","year":"2012","unstructured":"Larrain, S. & Rinella, M. E. A myriad of pathways to NASH. Clin. Liver Dis. 16, 525\u2013548 (2012).","journal-title":"Clin. Liver Dis."},{"key":"4680_CR4","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.taap.2015.08.022","volume":"289","author":"JD Schumacher","year":"2015","unstructured":"Schumacher, J. D. & Guo, G. L. Mechanistic review of drug-induced steatohepatitis. Toxicol. Appl. Pharmacol. 289, 40\u201347 (2015).","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"4680_CR5","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/hep.26319","volume":"58","author":"M Mouzaki","year":"2013","unstructured":"Mouzaki, M. et al. Intestinal microbiota in patients with nonalcoholic fatty liver disease. Hepatology 58, 120\u2013127 (2013).","journal-title":"Hepatology"},{"key":"4680_CR6","doi-asserted-by":"publisher","first-page":"1529","DOI":"10.1038\/s41598-017-01751-y","volume":"7","author":"D Zhou","year":"2017","unstructured":"Zhou, D. et al. Total fecal microbiota transplantation alleviates high-fat diet-induced steatohepatitis in mice via beneficial regulation of gut microbiota. Sci. Rep. 7, 1529 (2017).","journal-title":"Sci. Rep."},{"key":"4680_CR7","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1136\/gut.2005.071118","volume":"55","author":"K Tomita","year":"2006","unstructured":"Tomita, K. et al. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut 55, 415\u2013424 (2006).","journal-title":"Gut"},{"key":"4680_CR8","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1016\/j.bbamem.2007.08.017","volume":"1778","author":"H Chiba","year":"2008","unstructured":"Chiba, H., Osanai, M., Murata, M., Kojima, T. & Sawada, N. Transmembrane proteins of tight junctions. Biochim. Biophys. Acta 1778, 588\u2013600 (2008).","journal-title":"Biochim. Biophys. Acta"},{"key":"4680_CR9","unstructured":"Rao, J. N. & Wang, J. Y. in Regulation of Gastrointestinal Mucosal Growth (Morgan & Claypool Life Sciences, 2010) copyright \u00a92011 by Morgan & Claypool Life Sciences."},{"key":"4680_CR10","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nature06196","volume":"449","author":"N Barker","year":"2007","unstructured":"Barker, N. et al. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003\u20131007 (2007).","journal-title":"Nature"},{"key":"4680_CR11","doi-asserted-by":"publisher","first-page":"915","DOI":"10.1038\/ng.165","volume":"40","author":"E Sangiorgi","year":"2008","unstructured":"Sangiorgi, E. & Capecchi, M. R. Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40, 915\u2013920 (2008).","journal-title":"Nat. Genet."},{"key":"4680_CR12","doi-asserted-by":"publisher","first-page":"1099","DOI":"10.1038\/ncb2581","volume":"14","author":"JH van Es","year":"2012","unstructured":"van Es, J. H. et al. Dll1+ secretory progenitor cells revert to stem cells upon crypt damage. Nat. Cell Biol. 14, 1099\u20131104 (2012).","journal-title":"Nat. Cell Biol."},{"key":"4680_CR13","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1146\/annurev.physiol.010908.163145","volume":"71","author":"LG van der Flier","year":"2009","unstructured":"van der Flier, L. G. & Clevers, H. Stem cells, self-renewal, and differentiation in the intestinal epithelium. Annu. Rev. Physiol. 71, 241\u2013260 (2009).","journal-title":"Annu. Rev. Physiol."},{"key":"4680_CR14","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1083\/jcb.200704152","volume":"178","author":"P Bastide","year":"2007","unstructured":"Bastide, P. et al. Sox9 regulates cell proliferation and is required for Paneth cell differentiation in the intestinal epithelium. J. Cell Biol. 178, 635\u2013648 (2007).","journal-title":"J. Cell Biol."},{"key":"4680_CR15","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1083\/jcb.200806024","volume":"183","author":"S Liebner","year":"2008","unstructured":"Liebner, S. et al. Wnt\/beta-catenin signaling controls development of the blood-brain barrier. J. Cell Biol. 183, 409\u2013417 (2008).","journal-title":"J. Cell Biol."},{"key":"4680_CR16","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/168905","volume":"2015","author":"L Rabinowich","year":"2015","unstructured":"Rabinowich, L. & Shibolet, O. Drug induced steatohepatitis: An uncommon culprit of a common disease. BioMed Res. Int. 2015, 168905 (2015).","journal-title":"BioMed Res. Int."},{"key":"4680_CR17","doi-asserted-by":"publisher","first-page":"2005","DOI":"10.1002\/hep.25762","volume":"55","author":"N Chalasani","year":"2012","unstructured":"Chalasani, N. et al. The diagnosis and management of non-alcoholic fatty liver disease: Practice guideline by the American association for the study of liver diseases, American college of gastroenterology, and the American gastroenterological association. Hepatology 55, 2005\u20132023 (2012).","journal-title":"Hepatology"},{"key":"4680_CR18","doi-asserted-by":"publisher","first-page":"383","DOI":"10.3390\/md20060383","volume":"20","author":"J Feng","year":"2022","unstructured":"Feng, J. et al. Marine chitooligosaccharide alters intestinal flora structure and regulates hepatic inflammatory response to influence nonalcoholic fatty liver disease. Mar. Drugs 20, 383 (2022).","journal-title":"Mar. Drugs"},{"key":"4680_CR19","doi-asserted-by":"publisher","first-page":"9340316","DOI":"10.1155\/2018\/9340316","volume":"2018","author":"A Sobhonslidsuk","year":"2018","unstructured":"Sobhonslidsuk, A. et al. The association of gut microbiota with nonalcoholic steatohepatitis in Thais. BioMed Res. Int. 2018, 9340316 (2018).","journal-title":"BioMed Res. Int."},{"key":"4680_CR20","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.jhep.2017.11.014","volume":"68","author":"F Marra","year":"2018","unstructured":"Marra, F. & Svegliati-Baroni, G. Lipotoxicity and the gut-liver axis in NASH pathogenesis. J. Hepatol. 68, 280\u2013295 (2018).","journal-title":"J. Hepatol."},{"key":"4680_CR21","doi-asserted-by":"publisher","first-page":"11689","DOI":"10.3390\/ijms231911689","volume":"23","author":"T Kobayashi","year":"2022","unstructured":"Kobayashi, T., Iwaki, M., Nakajima, A., Nogami, A. & Yoneda, M. Current research on the pathogenesis of NAFLD\/NASH and the gut-liver axis: Gut microbiota, dysbiosis, and leaky-gut syndrome. Int. J. Mol. Sci. 23, 11689 (2022).","journal-title":"Int. J. Mol. Sci."},{"key":"4680_CR22","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1016\/j.jcmgh.2015.01.001","volume":"1","author":"J Luther","year":"2015","unstructured":"Luther, J. et al. Hepatic injury in nonalcoholic steatohepatitis contributes to altered intestinal permeability. Cell. Mol. Gastroenterol. Hepatol. 1, 222\u2013232 (2015).","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"4680_CR23","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2019.153039","volume":"63","author":"W Zhao","year":"2019","unstructured":"Zhao, W. et al. The combination of Ilexhainanoside D and ilexsaponin A1 reduces liver inflammation and improves intestinal barrier function in mice with high-fat diet-induced non-alcoholic fatty liver disease. Phytomedicine 63, 153039 (2019).","journal-title":"Phytomedicine"},{"key":"4680_CR24","doi-asserted-by":"publisher","first-page":"5125","DOI":"10.1038\/s41598-017-04989-8","volume":"7","author":"R Ahmad","year":"2017","unstructured":"Ahmad, R., Rah, B., Bastola, D., Dhawan, P. & Singh, A. B. Obesity-induces organ and tissue specific tight junction restructuring and barrier deregulation by Claudin switching. Sci. Rep. 7, 5125 (2017).","journal-title":"Sci. Rep."},{"key":"4680_CR25","doi-asserted-by":"publisher","first-page":"4969","DOI":"10.1242\/jcs.00165","volume":"115","author":"S Amasheh","year":"2002","unstructured":"Amasheh, S. et al. Claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells. J. Cell Sci. 115, 4969\u20134976 (2002).","journal-title":"J. Cell Sci."},{"key":"4680_CR26","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.gastro.2005.05.002","volume":"129","author":"F Heller","year":"2005","unstructured":"Heller, F. et al. Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions, apoptosis, and cell restitution. Gastroenterology 129, 550\u2013564 (2005).","journal-title":"Gastroenterology"},{"key":"4680_CR27","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1136\/gut.2006.094375","volume":"56","author":"S Zeissig","year":"2007","unstructured":"Zeissig, S. et al. Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn\u2019s disease. Gut 56, 61\u201372 (2007).","journal-title":"Gut"},{"key":"4680_CR28","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/S1590-8658(04)00094-5","volume":"36","author":"C Loguercio","year":"2004","unstructured":"Loguercio, C. et al. Non-alcoholic fatty liver disease: A multicentre clinical study by the Italian Association for the Study of the Liver. Dig. Liver Dis. 36, 398\u2013405 (2004).","journal-title":"Dig. Liver Dis."},{"key":"4680_CR29","doi-asserted-by":"publisher","first-page":"32","DOI":"10.3389\/fcimb.2013.00032","volume":"3","author":"I Zanoni","year":"2013","unstructured":"Zanoni, I. & Granucci, F. Role of CD14 in host protection against infections and in metabolism regulation. Front. Cell. Infect. Microbiol. 3, 32 (2013).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"4680_CR30","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.cmet.2012.05.012","volume":"16","author":"K Imajo","year":"2012","unstructured":"Imajo, K. et al. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling. Cell Metab. 16, 44\u201354 (2012).","journal-title":"Cell Metab."},{"key":"4680_CR31","doi-asserted-by":"publisher","first-page":"61","DOI":"10.3350\/cmh.2017.0030","volume":"24","author":"W Ando","year":"2018","unstructured":"Ando, W. et al. Serum matrix metalloproteinase-1 level represents disease activity as opposed to fibrosis in patients with histologically proven nonalcoholic steatohepatitis. Clin. Mol. Hepatol. 24, 61\u201376 (2018).","journal-title":"Clin. Mol. Hepatol."},{"key":"4680_CR32","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nature10408","volume":"478","author":"H Tian","year":"2011","unstructured":"Tian, H. et al. A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable. Nature 478, 255\u2013259 (2011).","journal-title":"Nature"},{"key":"4680_CR33","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1038\/s41419-017-0244-8","volume":"9","author":"F Deng","year":"2018","unstructured":"Deng, F. et al. YAP triggers the Wnt\/beta-catenin signalling pathway and promotes enterocyte self-renewal, regeneration and tumorigenesis after DSS-induced injury. Cell Death Dis. 9, 153 (2018).","journal-title":"Cell Death Dis."},{"key":"4680_CR34","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/j.stem.2013.11.008","volume":"14","author":"C Metcalfe","year":"2014","unstructured":"Metcalfe, C., Kljavin, N. M., Ybarra, R. & de Sauvage, F. J. Lgr5+ stem cells are indispensable for radiation-induced intestinal regeneration. Cell Stem Cell 14, 149\u2013159 (2014).","journal-title":"Cell Stem Cell"},{"key":"4680_CR35","doi-asserted-by":"publisher","DOI":"10.1099\/jmm.0.001930","volume":"74","author":"S Wei","year":"2025","unstructured":"Wei, S., Feng, Y., Meng, A., Ding, Z. & Lin, W. Altered gut microbial profiles in drug-treated rats with alcoholic heart disease. J. Med. Microbiol. 74, 001930 (2025).","journal-title":"J. Med. Microbiol."},{"key":"4680_CR36","doi-asserted-by":"publisher","first-page":"589","DOI":"10.2131\/jts.42.589","volume":"42","author":"S Sanoh","year":"2017","unstructured":"Sanoh, S. et al. Assessment of amiodarone-induced phospholipidosis in chimeric mice with a humanized liver. J. Toxicol. Sci. 42, 589\u2013596 (2017).","journal-title":"J. Toxicol. Sci."},{"key":"4680_CR37","first-page":"1573","volume":"88","author":"AP Vitins","year":"2014","unstructured":"Vitins, A. P. et al. Mechanisms of amiodarone and valproic acid induced liver steatosis in mouse in vivo act as a template for other hepatotoxicity models. Arch. Toxicol. 88, 1573\u20131588 (2014).","journal-title":"Arch. Toxicol."},{"key":"4680_CR38","doi-asserted-by":"publisher","first-page":"864","DOI":"10.1124\/jpet.104.072785","volume":"311","author":"TC McCarthy","year":"2004","unstructured":"McCarthy, T. C., Pollak, P. T., Hanniman, E. A. & Sinal, C. J. Disruption of hepatic lipid homeostasis in mice after amiodarone treatment is associated with peroxisome proliferator-activated receptor-alpha target gene activation. J. Pharmacol. Exp. Ther. 311, 864\u2013873 (2004).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"4680_CR39","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/BF00609891","volume":"24","author":"M St\u00e4ubli","year":"1983","unstructured":"St\u00e4ubli, M., Bircher, J., Galeazzi, R. L., Remund, H. & Studer, H. Serum concentrations of amiodarone during long term therapy. Relation to dose, efficacy and toxicity. Eur. J. Clin. Pharmacol. 24, 485\u2013494 (1983).","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"4680_CR40","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1002\/pds.668","volume":"11","author":"EP van Puijenbroek","year":"2002","unstructured":"van Puijenbroek, E. P. et al. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol. Drug Saf. 11, 3\u201310 (2002).","journal-title":"Pharmacoepidemiol. Drug Saf."},{"key":"4680_CR41","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1111\/1440-1681.12792","volume":"44","author":"S Kato","year":"2017","unstructured":"Kato, S. et al. Probiotic Bifidobacterium bifidum G9\u20131 attenuates 5-fluorouracil-induced intestinal mucositis in mice via suppression of dysbiosis-related secondary inflammatory responses. Clin. Exp. Pharmacol. Physiol. 44, 1017\u20131025 (2017).","journal-title":"Clin. Exp. Pharmacol. Physiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04680-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04680-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04680-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T03:04:06Z","timestamp":1751425446000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-025-04680-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":41,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4680"],"URL":"https:\/\/doi.org\/10.1038\/s41598-025-04680-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]},"assertion":[{"value":"16 January 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 July 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"23132"}}