{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T21:45:03Z","timestamp":1792100703366,"version":"4.4.0"},"reference-count":55,"publisher":"American Chemical Society (ACS)","issue":"33","license":[{"start":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T00:00:00Z","timestamp":1597190400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81370952"],"award-info":[{"award-number":["81370952"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81770864"],"award-info":[{"award-number":["81770864"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002338","name":"Ministry of Education of the People's Republic of China","doi-asserted-by":"publisher","award":["zrzd2017007"],"award-info":[{"award-number":["zrzd2017007"]}],"id":[{"id":"10.13039\/501100002338","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Epigallocatechin gallate (EGCG) has been regarded as a protective bioactive polyphenol in green tea against nonalcoholic steatohepatitis (NASH), but the mechanism remains poorly deciphered. Herein, we assessed the role and mechanism of EGCG on gut microbiota and the metabolism in NASH development. Forty-eight male C57BL\/6J mice were fed with either a methionine\u2013choline-sufficient diet or a methionine\u2013choline-deficient (MCD) diet with or without EGCG administration for 4 weeks. Liver injury, inflammation, lipid accumulation, and iron overload were examined. 16S ribosomal RNA sequencing was used to detect the fecal microbiome. In our research, we observed that EGCG notably improved MCD-diet-derived gut microbiota dysbiosis, as proved by a distinctively clustered separation from that of the MCD group and by the decrease of the Oxalobacter, Oscillibacter, Coprococcus_1, and Desulfovibrio genera and enrichment of norank_f__Bacteroidales_S24_7_group, Alloprevotella, and Bacteroides. Spearman-correlation heatmap analysis indicated that Bacteroides and Alloprevotella induced by EGCG were strongly negatively correlated with lipid accumulation. Functional enzymes of the gut microbiome were predicted by PICRUSt based on the operation classification unit. The results revealed that 1468 enzymes were involved in various metabolic pathways, and 371 enzymes showed distinct changes between untreated and EGCG-treated mice. Long-chain-fatty-acid-CoA ligase ACSBG played a distinct role in fatty acid metabolism and ferroptosis and was significantly negatively correlated with Bacteroides. Altogether, the salutary effect of EGCG on NASH might be via shifting gut flora and certain enzymes from genera. Our study thus takes a step toward NASH prevention and therapy.<\/jats:p>","DOI":"10.1021\/acsomega.0c01689","type":"journal-article","created":{"date-parts":[[2020,8,12]],"date-time":"2020-08-12T08:23:32Z","timestamp":1597220612000},"page":"20800-20809","source":"Crossref","is-referenced-by-count":69,"title":["Epigallocatechin Gallate Protects Mice against Methionine\u2013Choline-Deficient-Diet-Induced\nNonalcoholic Steatohepatitis by Improving Gut Microbiota To Attenuate\nHepatic Injury and Regulate Metabolism"],"prefix":"10.1021","volume":"5","author":[{"given":"Kaiting","family":"Ning","sequence":"first","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaikai","family":"Lu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Chen","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zizhen","family":"Guo","sequence":"additional","affiliation":[{"name":"Shanghai Jiao Tong University School of Medicine , ,","place":["Shanghai, P. R. China, 200025"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Du","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farooq","family":"Riaz","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lina","family":"Feng","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuping","family":"Fu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyan","family":"Yin","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University , , ,","place":["Xi\u2019an, China, 710004"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Litao","family":"Wu","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7808-1109","authenticated-orcid":true,"given":"Dongmin","family":"Li","sequence":"additional","affiliation":[{"name":"Xi\u2019an Jiaotong University Health Science Center , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]},{"name":"Ministry of Education of China , , , ,","place":["Xi\u2019an, Shaanxi, P. R. China, 710061"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,8,12]]},"reference":[{"key":"2026090202075775400_cit1","doi-asserted-by":"publisher","first-page":"15080","DOI":"10.1038\/nrdp.2015.80","article-title":"Nonalcoholic fatty liver disease","volume":"1","author":"Brunt","year":"2015","journal-title":"Nat. Rev. Dis. 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Ther."},{"key":"2026090202075775400_cit5","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/mog.0000000000000349","article-title":"Intestinal microbiota\nand nonalcoholic steatohepatitis","volume":"33","author":"Brandl","year":"2017","journal-title":"Curr. Opin.\nGastroenterol."},{"key":"2026090202075775400_cit6","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1177\/0884533615605811","article-title":"Role of the gut\nmicrobiome in nonalcoholic fatty liver\ndisease","volume":"30","author":"Aqel","year":"2015","journal-title":"Nutr. Clin. Pract."},{"key":"2026090202075775400_cit7","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.tem.2013.05.009","article-title":"Non-alcoholic steatohepatitis:\na\nmicrobiota-driven disease","volume":"24","author":"Moschen","year":"2013","journal-title":"Trends Endocrinol.\nMetab."},{"key":"2026090202075775400_cit8","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1016\/j.it.2018.05.002","article-title":"liver-Microbiome axis\nin Health and Disease","volume":"39","author":"Adolph","year":"2018","journal-title":"Trends Immunol."},{"key":"2026090202075775400_cit9","doi-asserted-by":"publisher","first-page":"15518","DOI":"10.3748\/wjg.v20.i42.15518","article-title":"Gut-liver axis and probiotics: their\nrole in non-alcoholic fatty\nliver disease","volume":"20","author":"Paolella","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"2026090202075775400_cit10","doi-asserted-by":"publisher","first-page":"5314","DOI":"10.2174\/1381612811319290011","article-title":"Gut-liver\naxis and microbiota in NAFLD: insight pathophysiology\nfor novel therapeutic target","volume":"19","author":"Miele","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"2026090202075775400_cit11","doi-asserted-by":"publisher","first-page":"311","DOI":"10.1016\/j.chom.2011.10.004","article-title":"Role of the commensal\nmicrobiota in normal and pathogenic\nhost immune responses","volume":"10","author":"Littman","year":"2011","journal-title":"Cell Host Microbe"},{"key":"2026090202075775400_cit12","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/nature10809","article-title":"Inflammasome-mediated\ndysbiosis regulates progression\nof NAFLD and obesity","volume":"482","author":"Henao-Mejia","year":"2012","journal-title":"Nature"},{"key":"2026090202075775400_cit13","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.it.2018.12.008","article-title":"The Intestinal Epithelium: Central Coordinator of Mucosal\nImmunity","volume":"40","author":"Allaire","year":"2019","journal-title":"Trends Immunol."},{"key":"2026090202075775400_cit14","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances\nthe intestinal barrier by facilitating tight junction assembly via\nactivation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"2026090202075775400_cit15","doi-asserted-by":"publisher","first-page":"G9","DOI":"10.1152\/ajpgi.00008.2012","article-title":"Liver cholesterol:\nis it playing possum in NASH?","volume":"303","author":"Farrell","year":"2012","journal-title":"Am. J. Physiol.:\nGastrointest. Liver Physiol."},{"key":"2026090202075775400_cit16","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1002\/hep.23229","article-title":"The plasma\nlipidomic signature of nonalcoholic steatohepatitis","volume":"50","author":"Puri","year":"2009","journal-title":"Hepatology"},{"key":"2026090202075775400_cit17","doi-asserted-by":"publisher","first-page":"424","DOI":"10.1158\/1055-9965.epi-08-0725","article-title":"Iron overload\nis associated with hepatic oxidative damage to DNA in nonalcoholic\nsteatohepatitis","volume":"18","author":"Fujita","year":"2009","journal-title":"Cancer Epidemiol., Biomarkers\nPrev."},{"key":"2026090202075775400_cit18","doi-asserted-by":"publisher","first-page":"4746","DOI":"10.3748\/wjg.v13.i35.4746","article-title":"Role of\niron in hepatic fibrosis:\none piece in the puzzle","volume":"13","author":"Philippe","year":"2007","journal-title":"World J. Gastroenterol."},{"key":"2026090202075775400_cit19","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/s0168-8278(02)00073-9","article-title":"In situ detection of lipid peroxidation\nand oxidative DNA damage in non-alcoholic fatty liver diseases","volume":"37","author":"Seki","year":"2002","journal-title":"J. Hepatol."},{"key":"2026090202075775400_cit20","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1111\/1751-2980.12431","article-title":"The Role of ADIPOQ Methylation in\nExperimental Non-alcoholic Fatty Liver Disease: ADIPOQ Methylation\nin NAFLD","volume":"17","author":"Chen","year":"2016","journal-title":"J. Dig. Dis."},{"key":"2026090202075775400_cit21","doi-asserted-by":"publisher","first-page":"S799","DOI":"10.1016\/s0016-5085(10)63684-0","article-title":"S1837 UDCA\nImproves Liver Inflammation of NASH by Reducing ROS Levels and Increasing\nthe Expression of NRF2-Regulated Antioxident Genes-an Examination\nUsing Hepatocyte-Specific PTEN Deficient Mice","volume":"138","author":"Ohshima","year":"2010","journal-title":"Gastroenterology"},{"key":"2026090202075775400_cit22","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1111\/j.1467-789x.2007.00389.x","article-title":"A short\nhistory of beverages and\nhow our body treats them","volume":"9","author":"Wolf","year":"2008","journal-title":"Obes. Rev."},{"key":"2026090202075775400_cit23","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1080\/07315724.2006.10719518","article-title":"Beneficial\neffects of green tea--a\nreview","volume":"25","author":"Cabrera","year":"2006","journal-title":"J. Am. Coll. Nutr."},{"key":"2026090202075775400_cit24","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1016\/j.lfs.2007.06.011","article-title":"Tea polyphenols for\nhealth promotion","volume":"81","author":"Khan","year":"2007","journal-title":"Life Sci."},{"key":"2026090202075775400_cit25","doi-asserted-by":"publisher","first-page":"487","DOI":"10.14670\/HH-23.487","article-title":"Tea\npolyphenols, their biological effects and potential\nmolecular targets","volume":"23","author":"Chen","year":"2008","journal-title":"Histol. Histopathol."},{"key":"2026090202075775400_cit26","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.phytochem.2008.11.011","article-title":"The potential role of green tea catechins in the prevention\nof the metabolic syndrome - a review","volume":"70","author":"Thielecke","year":"2009","journal-title":"Phytochemistry"},{"key":"2026090202075775400_cit27","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1038\/sj.ijo.0802926","article-title":"Epigallocatechin\ngallate attenuates diet-induced obesity in mice by decreasing energy\nabsorption and increasing fat oxidation","volume":"29","author":"Klaus","year":"2005","journal-title":"Int.\nJ. Obes."},{"key":"2026090202075775400_cit28","doi-asserted-by":"publisher","first-page":"373S","DOI":"10.1080\/07315724.2007.10719626","article-title":"Effects of\ngreen tea and EGCG on cardiovascular and metabolic health","volume":"26","author":"Wolfram","year":"2007","journal-title":"J. Am. Coll. 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Obes."},{"key":"2026090202075775400_cit31","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/aps.2015.11","article-title":"Green tea polyphenol\nepigallocatechin-3-gallate ameliorates insulin\nresistance in non-alcoholic fatty liver disease mice","volume":"36","author":"Gan","year":"2015","journal-title":"Acta Pharmacol. Sin."},{"key":"2026090202075775400_cit32","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.ejphar.2015.05.005","article-title":"Epigallocatechin gallate\nattenuated non-alcoholic steatohepatitis induced by methionine- and\ncholine-deficient diet","volume":"761","author":"Ding","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"2026090202075775400_cit33","doi-asserted-by":"publisher","first-page":"4703406","DOI":"10.1155\/2016\/4703406","article-title":"Gut Microbiota\nand Metagenomic Advancement in Digestive Disease","volume":"2016","author":"Yu","year":"2016","journal-title":"Gastroent. Res. Pract."},{"key":"2026090202075775400_cit34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.jhep.2014.10.023","article-title":"NAFLD incidence and\nremission: only a matter of weight\ngain and weight loss?","volume":"62","author":"Marchesini","year":"2015","journal-title":"J. Hepatol."},{"key":"2026090202075775400_cit35","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/j.canlet.2013.08.031","article-title":"Non-alcoholic steatohepatitis\nand preneoplastic lesions\ndevelop in the liver of obese and hypertensive rats: suppressing effects\nof EGCG on the development of liver lesions","volume":"342","author":"Kochi","year":"2014","journal-title":"Cancer Lett."},{"key":"2026090202075775400_cit36","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1111\/j.1748-1716.2009.01970.x","article-title":"AMP-activated protein kinase in the regulation of hepatic\nenergy metabolism: from physiology to therapeutic perspectives","volume":"196","author":"Viollet","year":"2009","journal-title":"Acta Physiol."},{"key":"2026090202075775400_cit37","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/nmeth.f.303","article-title":"QIIME allows analysis\nof high-throughput community sequencing data","volume":"7","author":"Caporaso","year":"2010","journal-title":"Nat. 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Biotechnol."},{"key":"2026090202075775400_cit41","doi-asserted-by":"publisher","first-page":"1967","DOI":"10.3389\/fmicb.2018.01967","article-title":"Butyrate\nProtects Mice Against Methionine\u2013Choline-Deficient Diet-Induced\nNon-alcoholic Steatohepatitis by Improving Gut Barrier Function, Attenuating\nInflammation and Reducing Endotoxin Levels","volume":"9","author":"Ye","year":"2018","journal-title":"Front. Microbiol."},{"key":"2026090202075775400_cit42","doi-asserted-by":"publisher","first-page":"17839","DOI":"10.3748\/wjg.v20.i47.17839","article-title":"Elevated\nfree cholesterol in a p62\noverexpression model of non-alcoholic steatohepatitis","volume":"20","author":"Simon","year":"2014","journal-title":"World J. 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