肠道菌群-Toll样受体轴与代谢相关脂肪性肝病的关系

孙媛媛; 张存正; 徐静远; 周春晓

doi:10.12449/JCH260625

肠道菌群-Toll样受体轴与代谢相关脂肪性肝病的关系

DOI: 10.12449/JCH260625

南京医科大学附属苏州医院消化内科，江苏苏州 215002

基金项目:

江苏省自然科学基金 (SBK20250408076)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：孙媛媛负责撰写论文；张存正负责论文设计；徐静远、周春晓负责指导文章撰写并最后定稿。

详细信息

通信作者:
周春晓， zhouchunxiao@njmu.edu.cn （ORCID： 0009-0006-6713-0944）

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出版历程
- 收稿日期: 2025-10-24
- 录用日期: 2025-11-19
- 出版日期: 2026-06-25

Association between the gut microbiota-Toll-like receptor axis and metabolic associated fatty liver disease

Department of Gastroenterology，Suzhou Hospital Affiliated to Nanjing Medical University，Suzhou，Jiangsu 215002，China

Research funding:

Jiangsu Provincial Natural Science Foundation (SBK20250408076)

More Information

Corresponding author: ZHOU Chunxiao， zhouchunxiao@njmu.edu.cn （ORCID： 0009-0006-6713-0944）

摘要

摘要: 代谢相关脂肪性肝病（MAFLD）的发病与肠道菌群紊乱密切相关。菌群失调可导致细菌衍生物（如脂多糖）易位，通过激活Toll样受体（TLR）及其下游信号通路，驱动肝脏炎症反应与代谢失衡。本文系统综述了肠道菌群-TLR在MAFLD中的作用机制，重点阐述了TLR2、TLR4等关键受体，以及TLR5、TLR7、TLR9等较少受关注成员的功能；总结了TLR激活后的下游信号事件，包括经典核因子κB、促分裂原活化的蛋白激酶通路，以及在MAFLD病理机制中日益受到关注的Janus激酶-信号转导与转录激活因子和磷脂酰肌醇3激酶-蛋白激酶B通路；最后归纳了以肠道菌群为靶点、通过调控肠道菌群-TLR信号轴治疗MAFLD的潜在干预策略，为临床防治提供了新思路。
- 代谢相关脂肪性肝病 /
- 胃肠道微生物组 /
- Toll样受体
Abstract: The pathogenesis of metabolic associated fatty liver disease （MAFLD） is closely associated with gut microbiota dysbiosis. Dysbiosis can lead to translocation of bacterial derivatives （such as lipopolysaccharide）， which drives hepatic inflammatory response and metabolic imbalance by activating Toll-like receptors （TLR） and their downstream signaling pathways. This article systematically reviews the mechanism of action of the gut microbiota-TLR axis in MAFLD， and elaborates on the function of the key receptors such as TLR2 and TLR4 and the lesser-studied members （TLR5， TLR7， and TLR9）. This article also summarizes the downstream signaling events after TLR activation， including the canonical NF-κB and MAPK pathways， as well as the role of the JAK-STAT and PI3K-Akt pathways in the pathological mechanism of MAFLD. Finally， this article reviews the potential intervention strategies for MAFLD by targeting gut microbiota and regulating the gut microbiota-TLR signaling axis， in order to provide new ideas for clinical prevention and treatment.
- Metabolic Associated Fatty Liver Disease /
- Gastrointestinal Microbiome /
- Toll-Like Receptor

HTML全文

注： MD2，髓样分化蛋白2；CD14，白细胞分化抗原14；TRIF，含有Toll/IL-1受体结构域的诱导干扰素β的衔接蛋白；TBK1，TANK结合激酶1；IRF3，干扰素调节因子3；IRF7，干扰素调节因子7；MYD88，髓系分化初级反应蛋白质88；TRAF6，肿瘤坏死因子受体相关因子6；TAK1，TGF-β激活激酶1；IKKα，核因子κB激酶亚基α抑制剂；IKKβ，核因子κB激酶亚基β抑制剂；IKKγ，核因子κB激酶亚基γ抑制剂；NF-κB，核因子κB；MAPK，促分裂原活化的蛋白激酶；AP-1，激活蛋白1；dsRNA，双链RNA；ssRNA，单链RNA；mtDNA，线粒体DNA；CpG DNA，胞嘧啶-磷酸-鸟嘌呤DNA；IL-6，白细胞介素6；IL-8，白细胞介素8；NLRP3，NOD样受体热蛋白结构域相关蛋白3；TNF-α，肿瘤坏死因子α；IL-17A，白细胞介素17A；IL-1β，白细胞介素1β；TLR，Toll样受体。

图 1 TLR活化后引起的下游通路

Figure 1. Downstream signaling pathways activated by TLR

下载: 全尺寸图片幻灯片

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