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We demonstrated that endogenous ethanol (EnEth) produced by intestinal microbiota is likely a causative agent of NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two mutants with different alcohol\u2010producing abilities, namely, W14\u2010<jats:italic>adh<\/jats:italic> and W14\u0394<jats:italic>adh<\/jats:italic>, were constructed using the clinical high alcohol\u2010producing (HiAlc) <jats:styled-content style=\"fixed-case\"><jats:italic>Klebsiella pneumoniae<\/jats:italic><\/jats:styled-content> strain W14 as a parent. Damage to hepatocytes caused by bacteria with different alcohol\u2010producing capacities was evaluated (EtOH group as positive control). The ultrastructural changes of mitochondria were assessed via transmission electron microscopy (TEM). Hepatic levels of mitochondrial reactive oxygen species (ROS), DNA damage, and adenosine triphosphate were examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results illustrated that steatosis was most severe in the W14\u2010<jats:italic>adh<\/jats:italic> group, followed by the W14 group, whereas the W14\u0394<jats:italic>adh<\/jats:italic> group had few fatty droplets. TEM and examination of related protein expression revealed that the mitochondrial integrity of HepG2 hepatocytes was considerably damaged in the EtOH and bacteria treatment groups. The impaired mitochondrial function in HepG2 hepatocytes was evidenced by reduced adenosine triphosphate content and increased mitochondrial ROS accumulation and DNA damage in the EtOH and bacteria treatment groups, especially the W14\u2010<jats:italic>adh<\/jats:italic> group. Meanwhile, liver injury and mitochondrial damage were observed in the hepatocytes of mice. The livers of mice in the W14\u2010<jats:italic>adh<\/jats:italic> group, which had the highest ethanol production, exhibited the most serious damage, similar to that in the EtOH group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>EnEth produced by HiAlc bacteria induces mitochondrial dysfunction in NAFLD.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.15027","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T12:44:46Z","timestamp":1583757886000},"page":"2009-2019","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":95,"title":["Endogenous ethanol produced by intestinal bacteria induces mitochondrial dysfunction in non\u2010alcoholic fatty liver disease"],"prefix":"10.1111","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4632-0811","authenticated-orcid":false,"given":"Xiao","family":"Chen","sequence":"first","affiliation":[{"name":"College of Food Science South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biobased Material and Green Papermaking Qilu University of Technology  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Li","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention, China PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiangtao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention, China PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Wei","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention, China PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weishi","family":"Lin","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention, China PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1413-7054","authenticated-orcid":false,"given":"Xiangna","family":"Zhao","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention, China PLA  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimin","family":"Jiang","sequence":"additional","affiliation":[{"name":"College of Food Science South China Agricultural University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Capital Institute of Pediatrics  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28431"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25762"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.10.027"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012615-044224"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-016-2161-x"},{"key":"e_1_2_5_7_1","first-page":"1200","article-title":"Obesity and female gender increase breath ethanol: potential implications for the pathogenesis of nonalcoholic steatohepatitis","volume":"96","author":"Nair S","year":"2001","journal-title":"Gastroenterol."},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26093"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.28572"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00361.2016"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.19267"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-012-2112-9"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22848"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2014.02.010"},{"key":"e_1_2_5_15_1","doi-asserted-by":"crossref","first-page":"554","DOI":"10.15288\/qjsa.1961.22.554","article-title":"Endogenous ethanol: a review","volume":"22","author":"Lester D","year":"1961","journal-title":"Q. 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