结直肠癌（CRC）是全球高发恶性肿瘤，胆汁酸代谢紊乱在其发生、发展中发挥重要作用。系统阐述胆汁酸的生理代谢过程，及其在CRC中的异常特征与调控机制。现有研究表明，CRC患者胆汁酸代谢呈现“次级升高、初级下降”的显著失调特征。胆汁酸代谢异常可通过代谢合成酶异常、肠道菌群失调、转运蛋白紊乱等多机制打破机体胆汁酸稳态，并进一步激活丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）、Wnt/β-连环蛋白（Wnt/β-catenin）等促癌通路。同时，胆汁酸受体法尼醇X受体（FXR）、G蛋白偶联胆汁酸受体5（TGR5），以及鞘氨醇-1-磷酸受体2（S1PR2）、孕烷X受体（PXR）、维生素D受体（VDR）等，可协同调控肿瘤细胞增殖、肠道炎症反应、肿瘤化疗敏感性及肿瘤微环境重塑。基于上述机制，从“代谢-转运-受体” 3个层面总结胆汁酸相关的CRC靶向干预策略，并分析当前研究中存在的关键问题。未来可结合单细胞多组学及肠道限制性药物等技术，深入解析胆汁酸调控CRC的分子机制、推动相关研究向临床转化。

Colorectal cancer (CRC) is a common malignancy worldwide, and bile acid metabolic disorders play an important role in its development and progression. This review systematically summarizes the physiological metabolism of bile acids and their abnormal characteristics and regulatory mechanisms in CRC. Patients with CRC exhibit a characteristic bile acid profile, marked by increased secondary bile acids and decreased primary bile acids. Dysregulated bile acid metabolism may disrupt bile acid homeostasis through multiple mechanisms involving synthetic enzymes, gut microbiota, and transport proteins, thereby activating pro-tumor signaling pathways such as mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) and Wnt/β-catenin. Bile acid receptors, including farnesoid X receptor (FXR), Takeda G protein-coupled bile acid receptor 5 (TGR5), sphingosine-1-phosphate receptor 2 (S1PR2), pregnane X receptor (PXR), and vitamin D receptor (VDR), collectively participate in the regulation of tumor cell proliferation, inflammatory responses, chemotherapy sensitivity, and the tumor microenvironment. Based on the above mechanisms, this review summarize bile acid-related targeted intervention strategies for CRC from three levels—metabolism, transport, and receptor—and analyze key challenges in current research. In the future, integrating single-cell multi-omics and gut-restricted drug delivery technologies could enable a deeper understanding of the molecular mechanisms by which bile acids regulate CRC, thereby accelerating the translation of these findings into clinical applications.

Q344.5;R285.5

国家自然科学基金项目（82274362）