噬菌体在代谢相关脂肪性肝病中的调控机制及治疗应用前景

罗泳珊; 陈慧婷

doi:10.12449/JCH260324

噬菌体在代谢相关脂肪性肝病中的调控机制及治疗应用前景

DOI: 10.12449/JCH260324

罗泳珊,
陈慧婷^, ,

广东医科大学第一临床医学院，广东湛江 524023

基金项目:

广州市医学重点学科建设项目（2025—2027年） ;

广州市临床重点专科（临床医学研究所）建设项目（2024—2026年）

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：罗泳珊负责收集及分析资料，撰写论文；陈慧婷负责拟定写作思路，指导撰写文章并最后定稿。

详细信息

通信作者:
陈慧婷， eychenhuiting@scut.edu.cn （ORCID： 0000-0003-0380-7822）

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出版历程
- 收稿日期: 2025-06-29
- 录用日期: 2025-09-25
- 出版日期: 2026-03-25

Regulatory mechanism of bacteriophages in metabolic dysfunction-associated fatty liver disease and their application prospects in treatment

Yongshan LUO,
Huiting CHEN^{,
,}

The First Clinical Medical College of Guangdong Medical University，Zhanjiang，Guangdong 524023，China

Research funding:

Project of Key Medical Discipline in Guangzhou （2025-2027） ;

Foundation of Guangzhou Key Clinical Specialties （Institute of Clinical Medicine）（2024-2026）

More Information

Corresponding author: CHEN Huiting， eychenhuiting@scut.edu.cn （ORCID： 0000-0003-0380-7822）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）是目前全球患病率最高的慢性肝病之一，迄今尚缺乏有效治疗方法。噬菌体作为肠道微生物群的重要组成部分，近年研究发现其可通过重塑菌群结构、调节肠屏障功能以及肠-肝轴信号传递，在MAFLD的病理进程中发挥关键作用。研究表明，MAFLD患者肠道噬菌体多样性下降，特定噬菌体的丰度与疾病严重程度密切相关。其潜在机制涉及噬菌体对肠道屏障功能的调节、对致病菌的靶向清除与有益菌的促定植作用，以及对免疫反应和炎症因子释放的调控。动物模型及临床前期试验显示，靶向干预噬菌体策略有望缓解肝脏炎症、改善脂肪变性及代谢紊乱。然而，噬菌体耐药性、宿主-噬菌体相互作用的复杂性及临床转化的安全性问题，仍是当前面临的挑战。本综述系统阐述了噬菌体在MAFLD中的调控机制及治疗应用前景，以期为该领域的后续研究及噬菌体疗法的开发提供理论参考。
- 代谢相关脂肪性肝病 /
- 细菌噬菌体 /
- 肠-肝轴
Abstract: Metabolic dysfunction-associated fatty liver disease （MAFLD） is one of the most prevalent chronic liver diseases worldwide， and currently there is still a lack of effective therapies. Bacteriophages are an important component of gut microbiota， and recent studies have shown that bacteriophages play a pivotal role in the pathological progression of MAFLD by reshaping microbiota structure， modulating intestinal barrier function， and regulating gut-liver axis signaling. Studies have also shown that there is a reduction in the diversity of bacteriophages in MAFLD patients， and the abundance of specific bacteriophages is closely associated with disease severity. The underlying mechanisms of bacteriophages involve the regulation of intestinal barrier， targeted clearance of pathogenic bacteria， promotion of the colonization of probiotic bacteria， and modulation of immune responses and the release of inflammatory cytokines. Animal models and preclinical trials have shown that targeted bacteriophage intervention strategies are expected to alleviate liver inflammation， improve steatosis， and ameliorate metabolic disorders. However， there are still challenges such as drug resistance of bacteriophage， the complexity of host-bacteriophage interactions， and safety issues in clinical translation. This article systematically elaborates on the regulatory mechanisms of bacteriophages in MAFLD and their application prospects in treatment， in order to provide a theoretical reference for future research and the development of bacteriophage-based therapies in this field.
- Metabolic Dysfunction-Associated Fatty Liver Disease /
- Bacteriophage /
- Gut-liver Axis

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注：噬菌体可通过特异性裂解、水平基因转移和编码毒力基因等方式，直接调控易感细菌的数量并改变肠道菌群结构；细菌特性与数量的变化又进一步影响代谢物的种类与总量，并通过级联效应作用于肠道共生细菌群落中的非目标细菌种类。

图 1 噬菌体影响肠道菌群

Figure 1. Bacteriophages influence the gut microbiota

下载: 全尺寸图片幻灯片

注：噬菌体穿透上皮屏障的机制主要包括4种途径：（1）噬菌体可直接穿过受损的上皮屏障进行迁移；（2）噬菌体可通过转胞吞作用被上皮细胞摄取；（3）隐藏在细菌中的噬菌体可以“特洛伊木马”机制穿越上皮屏障；（4）噬菌体也可被肠道树突状细胞摄入。

图 2 噬菌体穿透上皮屏障的机制

Figure 2. The mechanism of phage penetration through the mucosal barrier

下载: 全尺寸图片幻灯片

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