{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:40:28Z","timestamp":1792690828237,"version":"4.5.0"},"reference-count":104,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T00:00:00Z","timestamp":1632700800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013489","name":"Yakult Bio-Science Foundation","doi-asserted-by":"publisher","award":["2021"],"award-info":[{"award-number":["2021"]}],"id":[{"id":"10.13039\/501100013489","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19H04002"],"award-info":[{"award-number":["19H04002"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008886","name":"Princess Takamatsu Cancer Research Fund","doi-asserted-by":"publisher","award":["18\u201025003"],"award-info":[{"award-number":["18\u201025003"]}],"id":[{"id":"10.13039\/501100008886","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21cm0106401"],"award-info":[{"award-number":["JP21cm0106401"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21gm1010009"],"award-info":[{"award-number":["JP21gm1010009"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP21gm5010001"],"award-info":[{"award-number":["JP21gm5010001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gut microbiota and the mammalian host share a symbiotic relationship, in which the host provides a suitable ecosystem for the gut bacteria to digest indigestible nutrients and produce useful metabolites. Although gut microbiota primarily reside in and influence the intestine, they also regulate liver function via absorption and subsequent transfer of microbial components and metabolites through the portal vein to the liver. Due to this transfer, the liver may be continuously exposed to gut\u2010derived metabolites and components. For example, short\u2010chain fatty acids (SCFA) produced by gut microbiota, through the fermentation of dietary fiber, can suppress inflammation via regulatory T cell induction through SCFA\u2010induced epigenetic mechanisms. Additionally, secondary bile acids (BA), such as deoxycholic acid, produced by gut bacteria through the 7\u03b1\u2010dehydroxylation of primary BAs, are thought to induce DNA damage and contribute to the remodeling of tumor microenvironments. Other substances that are also thought to influence liver function include lipopolysaccharides (components of the outer membrane of gram\u2010negative bacteria) and lipoteichoic acid (cell wall component of Gram\u2010positive bacteria), which are ligands of innate immune receptors, Toll\u2010like receptor\u20104, and Toll\u2010like receptor\u20102, respectively, through which inflammatory signaling is elicited. In this review, we focus on the role of gut microbiota in the liver microenvironment, describing the anatomy of the gut\u2010liver axis, the role of gut microbial metabolites, and the relationships that exist between gut microbiota and liver diseases, including liver cancer.<\/jats:p>","DOI":"10.1111\/cas.15142","type":"journal-article","created":{"date-parts":[[2021,9,17]],"date-time":"2021-09-17T13:35:11Z","timestamp":1631885711000},"page":"4433-4443","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Gut\u2010liver axis\u2010mediated mechanism of liver cancer: A special focus on the role of gut microbiota"],"prefix":"10.1111","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-0797","authenticated-orcid":false,"given":"Naoko","family":"Ohtani","sequence":"first","affiliation":[{"name":"Department of Pathophysiology Graduate School of Medicine Osaka City University Osaka Japan"},{"name":"AMED\u2010CREST AMED Japan Agency for Medical Research and Development Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Hara","sequence":"additional","affiliation":[{"name":"Research Institute for Microbial Diseases Osaka University Suita Japan"},{"name":"Immunology Frontier Research Center (IFReC) Osaka University Suita Japan"},{"name":"Center for Infectious Disease Education and Research (CiDER) Osaka University Suita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2016.1182295"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R116.752899"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-316307"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2691"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1219451110"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms6040107"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1331"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.livres.2017.11.005"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/advances\/nmz061"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i9.923"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.169"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000063817"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)02169-3"},{"key":"e_1_2_15_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5134"},{"key":"e_1_2_15_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12041082"},{"key":"e_1_2_15_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2019-00481"},{"key":"e_1_2_15_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.604179"},{"key":"e_1_2_15_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.564768"},{"key":"e_1_2_15_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21060"},{"key":"e_1_2_15_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2977-2"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00990"},{"key":"e_1_2_15_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13193"},{"key":"e_1_2_15_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_15_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.06.049"},{"key":"e_1_2_15_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12347"},{"key":"e_1_2_15_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0000000000000057"},{"key":"e_1_2_15_28_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900010-JLR200"},{"key":"e_1_2_15_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2014.04.016"},{"key":"e_1_2_15_30_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i33.7463"},{"key":"e_1_2_15_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1365"},{"key":"e_1_2_15_32_1","doi-asserted-by":"publisher","DOI":"10.1081\/DMR-200033475"},{"key":"e_1_2_15_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.27635"},{"key":"e_1_2_15_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1323599111"},{"key":"e_1_2_15_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan5931"},{"key":"e_1_2_15_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ueg2.12062"},{"key":"e_1_2_15_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.03.039"},{"key":"e_1_2_15_38_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2019.11.312"},{"key":"e_1_2_15_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-012-2112-9"},{"key":"e_1_2_15_40_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308379"},{"key":"e_1_2_15_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26093"},{"key":"e_1_2_15_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572-0241.2001.03702.x"},{"key":"e_1_2_15_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2019.08.018"},{"key":"e_1_2_15_44_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2017.1357534"},{"key":"e_1_2_15_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2018.05.003"},{"key":"e_1_2_15_46_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0903670"},{"key":"e_1_2_15_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccell.2018.02.005"},{"key":"e_1_2_15_48_1","doi-asserted-by":"publisher","DOI":"10.1158\/1541-7786.MCR-18-0362"},{"key":"e_1_2_15_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0370-y"},{"key":"e_1_2_15_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(19)30274-8"},{"key":"e_1_2_15_51_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-018-0702-0"},{"key":"e_1_2_15_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-019-0664-6"},{"key":"e_1_2_15_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.07.038"},{"key":"e_1_2_15_54_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00640"},{"key":"e_1_2_15_55_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2018-317232"},{"key":"e_1_2_15_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-0764-0"},{"key":"e_1_2_15_57_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2018.1461300"},{"key":"e_1_2_15_58_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-08711-2"},{"key":"e_1_2_15_59_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7042839"},{"key":"e_1_2_15_60_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1016088108"},{"key":"e_1_2_15_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2852"},{"key":"e_1_2_15_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12721"},{"key":"e_1_2_15_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.004"},{"key":"e_1_2_15_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2018.10.009"},{"key":"e_1_2_15_65_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-25965-x"},{"key":"e_1_2_15_66_1","first-page":"320","article-title":"Formation of methylamines from ingested choline and lecithin","volume":"225","author":"Zeisel SH","year":"1983","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_15_67_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.02481-14"},{"key":"e_1_2_15_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09922"},{"key":"e_1_2_15_69_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1093\/advances\/nmz064","article-title":"The gut microbial metabolite trimethylamine N\u2010oxide and hypertension risk: a systematic review and dose\u2010response meta\u2010analysis","volume":"11","author":"Ge X","year":"2020","journal-title":"Adv Nutr"},{"key":"e_1_2_15_70_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCINTERVENTIONS.118.007281"},{"key":"e_1_2_15_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-018-0091-y"},{"key":"e_1_2_15_72_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2011.09.009"},{"key":"e_1_2_15_73_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1742-x"},{"key":"e_1_2_15_74_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI90562"},{"key":"e_1_2_15_75_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1506330"},{"key":"e_1_2_15_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0333-1"},{"key":"e_1_2_15_77_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0058-x"},{"key":"e_1_2_15_78_1","first-page":"1935","article-title":"Role and effective therapeutic target of gut microbiota in NAFLD\/NASH","volume":"18","author":"Liu Q","year":"2019","journal-title":"Exp Ther Med"},{"key":"e_1_2_15_79_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijcp.13947"},{"key":"e_1_2_15_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jceh.2018.08.006"},{"key":"e_1_2_15_81_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-012-9360-9"},{"key":"e_1_2_15_82_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.13058"},{"key":"e_1_2_15_83_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i42.9346"},{"key":"e_1_2_15_84_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22848"},{"key":"e_1_2_15_85_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-010-1447-3"},{"key":"e_1_2_15_86_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2019.05.029"},{"key":"e_1_2_15_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature16969"},{"key":"e_1_2_15_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.08.016"},{"key":"e_1_2_15_89_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.007"},{"key":"e_1_2_15_90_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23845"},{"key":"e_1_2_15_91_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature24302"},{"key":"e_1_2_15_92_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-16-0932"},{"key":"e_1_2_15_93_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-009-0112-0"},{"key":"e_1_2_15_94_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.14937"},{"key":"e_1_2_15_95_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.14867"},{"key":"e_1_2_15_96_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan4236"},{"key":"e_1_2_15_97_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aao3290"},{"key":"e_1_2_15_98_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aan3706"},{"key":"e_1_2_15_99_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abb5920"},{"key":"e_1_2_15_100_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abf3363"},{"key":"e_1_2_15_101_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.655697"},{"key":"e_1_2_15_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3547"},{"key":"e_1_2_15_103_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.046"},{"key":"e_1_2_15_104_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.07.006"},{"key":"e_1_2_15_105_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2425-3"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.15142","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.15142","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.15142","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T22:07:20Z","timestamp":1692655640000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.15142"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,27]]},"references-count":104,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2021,11]]}},"alternative-id":["10.1111\/cas.15142"],"URL":"https:\/\/doi.org\/10.1111\/cas.15142","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,27]]},"assertion":[{"value":"2021-08-19","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}