{ "abstract": "The role of intrahepatic microbiome in hepatocellular carcinoma (HCC) remains elusive. In this study, we profiled matched gut and intrahepatic microbiomes from patients with HCC and healthy subjects. Compared with healthy subjects, we observed increased gut–liver microbiome similarity and a gut pathobiont–centered network in HCC, implying microbial transfer via the gut–liver axis. Consistently, HCC stool transplantation to germ-free mice impaired gut barrier function and increased bacterial load in the liver. Multisite analysis of intrahepatic microbiome and host transcriptome revealed that gut pathobionts in tumor regions positively correlate with host cytokine expression and oncogenic pathways. Administration of HCC-enriched Bacteroides fragilis disrupted gut barrier in mice and led to live bacteria translocation to the liver. B. fragilis exacerbated liver damage and promoted HCC development in mice. Mechanistically, B. fragilis surface protein enolase interacts with and activates vimentin on hepatocytes, triggering oncogenic cascades. Our findings provide insight into how gut pathobionts translocate to the liver to promote hepatocarcinogenesis.\n\nSignificance:: Parallel characterization of stool and intrahepatic microbiomes from patients with HCC and healthy subjects revealed gut–liver microbial transfer. The gut pathobiont B. fragilis disrupts gut barrier and translocates as live bacteria to the liver. Its surface protein enolase binds hepatocyte vimentin to activate proinflammatory and oncogenic signaling, thereby promoting liver tumorigenesis.\n\nSee related commentary by Chojnacka and Grivennikov, p. 2214", "abstract_shown": true, "affiliations": [ "Institute of Digestive Disease and The Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China.", "Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "Department of Oncology, Cancer Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "Department of Liver Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.", "Advanced Medical Technology Centre, The First Affiliated Hospital, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.", "Clinical Trials Unit, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.", "Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China." ], "article_type": "research article", "arxiv": null, "author_total": 23, "authors": [ { "affs": [ 0 ], "name": "Weixin Liu", "orcid": "0000-0002-1650-0371" }, { "affs": [ 0 ], "name": "Xueliang Wang", "orcid": "0009-0006-0324-6518" }, { "affs": [ 1, 2 ], "name": "Ying Zhang", "orcid": "0000-0002-5545-5294" }, { "affs": [ 0, 3 ], "name": "Jinkai Liu", "orcid": "0009-0005-8989-0103" }, { "affs": [ 0 ], "name": "Meiyi Li", "orcid": "0000-0002-9309-6149" }, { "affs": [ 1 ], "name": "Qianying Zhou", "orcid": "0009-0001-7486-0295" }, { "affs": [ 1 ], "name": "Lina Wang", "orcid": "0009-0002-1649-0756" }, { "affs": [ 1 ], "name": "Shimao Liu", "orcid": "0009-0006-7292-882X" }, { "affs": [ 1 ], "name": "Weikang Chen", "orcid": "0009-0007-8992-6190" }, { "affs": [ 0 ], "name": "Eagle S.H. Chu", "orcid": "0000-0002-3947-8808" }, { "affs": [ 0 ], "name": "Harry Cheuk-Hay Lau", "orcid": "0000-0003-3581-2909" }, { "affs": [ 0 ], "name": "Qian Song", "orcid": "0000-0001-6545-8926" }, { "affs": [ 0 ], "name": "Xingyu Zhou", "orcid": "0009-0005-7988-5853" }, { "affs": [ 0 ], "name": "Hongyan Gou", "orcid": "0000-0002-3446-6402" }, { "affs": [ 0 ], "name": "Jennifer Xiang Zhang", "orcid": "0000-0002-3222-5824" }, { "affs": [ 4 ], "name": "Guo-Bao Tian", "orcid": "0000-0001-6750-5482" }, { "affs": [ 5 ], "name": "Liangjing Wang", "orcid": "0000-0001-8227-8855" }, { "affs": [ 1 ], "name": "Xiaoxing Li", "orcid": "0000-0001-8791-7505" }, { "affs": [ 1, 5 ], "name": "Sui Peng", "orcid": "0000-0002-7399-2579" }, { "affs": [ 0 ], "name": "Chi Chun Wong", "orcid": "0000-0003-1362-3541" }, { "affs": [ 1, 6 ], "name": "Ming Kuang", "orcid": "0000-0002-7397-5779" }, { "affs": [ 1, 2 ], "name": "Lixia Xu", "orcid": "0000-0002-1818-6267" }, { "affs": [ 0, 1 ], "name": "Jun Yu", "orcid": "0000-0001-5008-2153" } ], "bibtex": "https://research.draconitic.com/paper/bh3m132y2nwsm.bib", "cited_by": 2, "doi": "10.1158/2159-8290.cd-25-1355", "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13725344/", "id": "bh3m132y2nwsm", "issns": [ "2159-8274", "2159-8290" ], "landing_url": "https://doi.org/10.1158/2159-8290.cd-25-1355", "language": "en", "licence": "CC-BY-NC-ND-4.0", "licence_label": "CC BY-NC-ND 4.0", "licence_source": "article", "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/", "metadata_licence": null, "native_subjects": [ [ "heading", "Carcinogenesis" ], [ "heading", "Research Articles" ], [ "heading", "Tumor Initiation and Promotion" ], [ "openalex", "1312|Gut microbiota and health" ] ], "openalex": "W7163526704", "pdf_url": null, "pmcid": "PMC13725344", "pmid": "42240277", "published": "2026-06-04", "publisher": null, "ris": "https://research.draconitic.com/paper/bh3m132y2nwsm.ris", "sources": [ { "first_seen": "2026-11-04T12:23:45Z", "native_id": "PMC13725344", "source": "pmc", "url": "https://doi.org/10.1158/2159-8290.cd-25-1355" } ], "subjects": [ { "field": "biochemistry", "origin": "openalex:1312|Gut microbiota and health", "subfield": "molecular-biology" } ], "title": "Gut Pathobionts Translocate into the Liver and Reshape Intrahepatic Microbiome to Facilitate Hepatocellular Carcinoma", "title_text": "Gut Pathobionts Translocate into the Liver and Reshape Intrahepatic Microbiome to Facilitate Hepatocellular Carcinoma", "type": "peer-reviewed", "updated_at": "2026-11-06T12:21:38Z", "url": "https://research.draconitic.com/paper/bh3m132y2nwsm", "venue": "Cancer Discovery", "versions": [] }