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REVIEW article

Front. Immunol.

Sec. Microbial Immunology

This article is part of the Research TopicApplication of Novel Biomarkers and Natural Compounds in Precision OncologyView all 10 articles

Gut Microbiome, a Novel Precision Medicine Biomarker for Hepatocellular Carcinoma

Provisionally accepted
Pin-Jung ChenPin-Jung Chen1,2Suzanne DevkotaSuzanne Devkota3,4Stephen Lawrence ShiaoStephen Lawrence Shiao5Andrew Eugene HendifarAndrew Eugene Hendifar2Ju Dong YangJu Dong Yang4*
  • 1Cedars Sinai Medical Center, Los Angeles, United States
  • 2Department of Hematology/Oncology, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, United States
  • 3Human Microbiome Research Institute, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, United States
  • 4Karsh Division of Gastroenterology and Hepatology, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, United States
  • 5Department of Radiation Oncology, Cedars-Sinai Medical Center, Los Angeles, Los Angeles, United States

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Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors (ICIs) have transformed systemic therapy, durable responses are achieved in only a subset of patients, highlighting the need for reliable predictive biomarkers. The gut–liver axis, a bidirectional network linking intestinal microbiota, microbial metabolites, and hepatic immune pathways, has emerged as a key regulator of liver immunity and tumor progression. Growing evidence indicates that the gut microbiome modulates ICI efficacy by shaping immune activation, cytokine signaling, and drug metabolism. This review summarizes current insights into how gut microbial composition and metabolites influence immunotherapy outcomes in HCC and discusses microbiome-targeted strategies, including fecal microbiota transplantation (FMT), prebiotics, probiotics, and dietary interventions. Further research and clinical validation are needed before these insights can be effectively integrated into HCC management.

Keywords: Gut micobiome, Hepatocellualr carcinoma, Immunotherapy, Gut-liver axis, Presicion Oncology

Received: 22 Feb 2025; Accepted: 24 Nov 2025.

Copyright: © 2025 Chen, Devkota, Shiao, Hendifar and Yang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Ju Dong Yang

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material