肠道菌群稳态在肝细胞癌发生发展中的作用及相关靶向干预策略

崔艳; 焦俊喆; 闫瑞娟; 闫曙光; 魏海梁; 常占杰; 张海博; 李京涛

doi:10.12449/JCH250930

肠道菌群稳态在肝细胞癌发生发展中的作用及相关靶向干预策略

DOI: 10.12449/JCH250930

1.
陕西中医药大学第一临床医学院，陕西咸阳 712000
2.
陕西中医药大学附属医院肝病一科，陕西咸阳 712000

基金项目:

国家自然科学基金 (82174330);

国家自然科学基金 (82374418);

陕西省科技厅科研基金 (2024JC-YBMS-650);

陕西省科技厅科研基金 (2024SF-YBXM-528);

陕西省科技厅创新团队 (2022TD-55);

陕西省中医药管理局 (SZY-KJCYC-2023-049);

陕西省中医药管理局 (SZY-KJCYC-2023-087);

陕西省中医药管理局“双链融合”创新团队 (2022-SLRH-LJ-002)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：崔艳负责设计课题，分析资料，撰写论文；焦俊喆、闫瑞娟、闫曙光、魏海梁参与收集数据，修改论文；常占杰、张海博、李京涛负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
李京涛， lijingtao555@163.com （ORCID： 0000-0002-9286-2542）

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出版历程
- 收稿日期: 2025-01-17
- 录用日期: 2025-03-14
- 出版日期: 2025-09-25

The role of gut microbiota homeostasis in the occurrence and development of hepatocellular carcinoma and targeted intervention strategies

1.
The First Clinical Medical College，Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712000，China
2.
First Department of Liver Disease，The Affiliated Hospital of Shaanxi University of Chinese Medicine，Xianyang，Shaanxi 712000，China

Research funding:

National Natural Science Foundation of China (82174330);

National Natural Science Foundation of China (82374418);

Shaanxi Province Science and Technology Department Research Fund (2024JC-YBMS-650);

Shaanxi Province Science and Technology Department Research Fund (2024SF-YBXM-528);

Shaanxi Province Science and Technology Department Innovation Team (2022TD-55);

Shaanxi Province Traditional Chinese Medicine Administration (SZY-KJCYC-2023-049);

Shaanxi Province Traditional Chinese Medicine Administration (SZY-KJCYC-2023-087);

Shaanxi Province Traditional Chinese Medicine Administration “Dual Chain Integration” Innovation Team (2022-SLRH-LJ-002)

More Information

Corresponding author: LI Jingtao， lijingtao555@163.com （ORCID： 0000-0002-9286-2542）

摘要

摘要: 肝细胞癌（HCC）作为全球第六大常见恶性肿瘤，其隐匿性发病特征和高死亡率对人类健康构成严重威胁。本文综述肠道菌群（GM）稳态在HCC发生发展中的分子机制与干预策略，旨在为HCC的干预和治疗提供新思路。GM失调、肠渗漏、微生物相关分子模式、细菌易位及代谢产物等在HCC进展中发挥关键作用。GM失衡可能导致免疫逃逸，进而促进肿瘤细胞增殖和转移。本文详细论述GM与HCC的关系，深入分析GM在HCC发生发展中的作用机制，研究胆汁酸相关代谢产物、短链脂肪酸相关代谢产物及其他代谢产物在HCC中的作用，并探讨靶向GM治疗HCC的策略，包括益生菌、益生元、抗生素和Toll样受体4拮抗剂的使用及粪便微生物群移植等方法。本文强调，维护肠道屏障完整和GM稳态在HCC防治中具有重要意义，为开发新的诊疗策略提供方向。
- 癌，肝细胞 /
- 胃肠道微生物组 /
- 治疗学
Abstract: Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.
- Carcinoma， Hepatocellular /
- Gastrointestinal Microbiome /
- Therapeutics

HTML全文

注： BA，胆汁酸；FMT，粪便微生物群移植；TLR4，Toll样受体4；GM，肠道菌群；MAMP，微生物相关分子模式；LPS，脂多糖；HSC，肝星状细胞；TME，肿瘤微环境；NF-κB，核因子κB；HCC，肝细胞癌；SCFA，短链脂肪酸；FXR，法尼醇X受体；TGR5，武田G蛋白偶联受体5。

图 1 GM与HCC的关系

Figure 1. The relationship between GM and HCC

下载: 全尺寸图片幻灯片

表 1 不同代谢产物在HCC中的机制及作用

Table 1. The mechanism and role of different metabolites in HCC

代谢产物	机制	作用	参考文献
吲哚-3-乙酸	通过诱导血红素加氧酶1的表达以及直接清除自由基发挥作用	减轻RAW264.7巨噬细胞中的炎症反应和自由基产生	［39］
吲哚-3-乙酸	在非酒精性脂肪性肝病的研究中，IAA通过缓解肝脏脂肪生成、氧化应激和炎症反应发挥作用	减轻小鼠的肝损伤	［40］
吲哚丙酸	在非酒精性脂肪性肝病的研究中，增强线粒体氧化磷酸化作用	改善线粒体呼吸缺陷	［41］
多氨	与mTOR和RAS等致癌信号通路存在交叉作用	可能成为癌症治疗的潜在靶点	［42］
精氨酸	精氨酸耗竭	诱导HCC细胞死亡	［43］
	通过RNA结合基序蛋白39控制代谢基因的表达	促进肿瘤形成	［44］
	L-精氨酸和5-FU联合应用可通过iNOS/NO/AKT途径抑制有氧糖酵解酶，从而抑制糖代谢	抑制HCC细胞的糖代谢	［45］
亚精胺	激活微管相关蛋白1S介导的自噬，缓解自噬中的癌细胞缺陷	预防肝纤维化和HCC	［46］
亚精胺	通过在mRNA和蛋白水平上减少细胞外基质蛋白水平以及增加HSC中脂滴数量发挥作用	抑制HSC的活化	［47］
甲烷	通过激活PI3K/AKT/GSK-3β信号通路上调IL-10的表达	抑制NF-κB和MAPK信号通路	［48］
硫化氢	调节3-巯基丙酮酸硫转移酶酶的表达	双向调节HCC进展	［49］

下载: 导出CSV

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