Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma

The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabo...

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Main Authors: Siqi Ren, Yinping Zhang, Xingyue Wang, Jiahong Su, Xiang Wang, Zijun Yuan, Xinyu He, Sipeng Guo, Yu Chen, Shuai Deng, Xu Wu, Mingxing Li, Fukuan Du, Yueshui Zhao, Jing Shen, Wei Hu, Xiaobing Li, Zhangang Xiao
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-02-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526967/full
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author Siqi Ren
Yinping Zhang
Xingyue Wang
Jiahong Su
Xiang Wang
Zijun Yuan
Xinyu He
Sipeng Guo
Yu Chen
Yu Chen
Yu Chen
Shuai Deng
Shuai Deng
Shuai Deng
Xu Wu
Xu Wu
Xu Wu
Mingxing Li
Mingxing Li
Mingxing Li
Fukuan Du
Fukuan Du
Fukuan Du
Yueshui Zhao
Yueshui Zhao
Yueshui Zhao
Jing Shen
Jing Shen
Jing Shen
Wei Hu
Xiaobing Li
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
author_facet Siqi Ren
Yinping Zhang
Xingyue Wang
Jiahong Su
Xiang Wang
Zijun Yuan
Xinyu He
Sipeng Guo
Yu Chen
Yu Chen
Yu Chen
Shuai Deng
Shuai Deng
Shuai Deng
Xu Wu
Xu Wu
Xu Wu
Mingxing Li
Mingxing Li
Mingxing Li
Fukuan Du
Fukuan Du
Fukuan Du
Yueshui Zhao
Yueshui Zhao
Yueshui Zhao
Jing Shen
Jing Shen
Jing Shen
Wei Hu
Xiaobing Li
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
author_sort Siqi Ren
collection DOAJ
description The gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.
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record_format Article
series Frontiers in Immunology
spelling doaj-art-da0608468a424d90b3c7eca7eaa388da2025-08-20T02:15:34ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-02-011610.3389/fimmu.2025.15269671526967Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinomaSiqi Ren0Yinping Zhang1Xingyue Wang2Jiahong Su3Xiang Wang4Zijun Yuan5Xinyu He6Sipeng Guo7Yu Chen8Yu Chen9Yu Chen10Shuai Deng11Shuai Deng12Shuai Deng13Xu Wu14Xu Wu15Xu Wu16Mingxing Li17Mingxing Li18Mingxing Li19Fukuan Du20Fukuan Du21Fukuan Du22Yueshui Zhao23Yueshui Zhao24Yueshui Zhao25Jing Shen26Jing Shen27Jing Shen28Wei Hu29Xiaobing Li30Zhangang Xiao31Zhangang Xiao32Zhangang Xiao33Zhangang Xiao34Zhangang Xiao35Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaResearch and Experiment Center, Sichuan College of Traditional Chinese Medicine, Mianyang, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaDepartment of Gastroenterology, Shenzhen Hospital, Southern Medical University, Shenzhen, Guangdong, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, ChinaResearch and Experiment Center, Sichuan College of Traditional Chinese Medicine, Mianyang, ChinaCell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, ChinaSouth Sichuan Institute of Translational Medicine, Luzhou, ChinaGulin Traditional Chinese Medicine Hospital, Luzhou, ChinaThe gut microbiota, a complex microbial ecosystem closely connected to the liver via the portal vein, has emerged as a critical regulator of liver health and disease. Numerous studies have underscored its role in the onset and progression of liver disorders, including alcoholic liver disease, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction-associated steatohepatitis (MASH), liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). This review provides a comprehensive overview of current insights into the influence of the gut microbiota on HCC progression, particularly its effects on immune cells within the HCC tumor microenvironment (TME). Furthermore, we explore the potential of gut microbiota-targeted interventions, such as antibiotics, probiotics, prebiotics, and fecal microbiota transplantation (FMT), to modulate the immune response and improve outcomes of immunotherapy in HCC. By synthesizing insights from recent studies, this review aims to highlight microbiota-based strategies that may enhance immunotherapy outcomes, advancing personalized approaches in HCC treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526967/fullgut microbiotahepatocellular carcinoma (HCC)tumor microenvironment (TME)antibioticsprobioticsprebiotics
spellingShingle Siqi Ren
Yinping Zhang
Xingyue Wang
Jiahong Su
Xiang Wang
Zijun Yuan
Xinyu He
Sipeng Guo
Yu Chen
Yu Chen
Yu Chen
Shuai Deng
Shuai Deng
Shuai Deng
Xu Wu
Xu Wu
Xu Wu
Mingxing Li
Mingxing Li
Mingxing Li
Fukuan Du
Fukuan Du
Fukuan Du
Yueshui Zhao
Yueshui Zhao
Yueshui Zhao
Jing Shen
Jing Shen
Jing Shen
Wei Hu
Xiaobing Li
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Zhangang Xiao
Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
Frontiers in Immunology
gut microbiota
hepatocellular carcinoma (HCC)
tumor microenvironment (TME)
antibiotics
probiotics
prebiotics
title Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
title_full Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
title_fullStr Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
title_full_unstemmed Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
title_short Emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
title_sort emerging insights into the gut microbiota as a key regulator of immunity and response to immunotherapy in hepatocellular carcinoma
topic gut microbiota
hepatocellular carcinoma (HCC)
tumor microenvironment (TME)
antibiotics
probiotics
prebiotics
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1526967/full
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