肠道微生物组与内分泌轴的对话：从机制解析 到精准医疗新范式

Dialogue between the Gut Microbiota and the Endocrine Axis: From Mechanistic Insights to a New Paradigm for Precision Medicine

摘要: 肠道微生物组作为人体的“虚拟内分泌器官”，通过产生代谢产物、调节免疫反应和影响神经信号等多种机制，与宿主的内分泌系统进行广泛而深刻的双向对话。这种对话不仅构成了维持宿主能量代谢、应激反应和生殖功能稳态的基础，其失衡更是关系到肥胖、2型糖尿病、多囊卵巢综合征、非酒精性脂肪性肝病及神经内分泌疾病等疾病的核心驱动因素之一。本文旨在系统综述肠–胰岛轴、肠–脑轴(通过HPA轴)、肠–性腺轴及肠–脂肪轴等主要对话轴线的分子与细胞机制，首先阐述微生物衍生信号分子(如短链脂肪酸、次级胆汁酸、色氨酸代谢物)在内分泌调控中的核心作用。进一步，本文将总结基于微生物组的诊断生物标志物研究现状，以及粪菌移植、精准益生菌、微生物组工程等新兴治疗策略的潜力和挑战。最后，对未来研究方向，包括因果关系的深度解析、个体化干预方案的制定及微生物组–内分泌轴在精准医疗中的整合应用进行展望。理解并干预肠道微生物组与内分泌轴的对话，将为一系列内分泌代谢疾病的防治提供革命性的新视角和新策略。

Abstract: The gut microbiota, functioning as a “virtual endocrine organ” in the human body, engages in extensive and profound bidirectional communication with the host’s endocrine system through various mechanisms such as producing metabolites, regulating immune responses, and influencing neural signaling. This dialogue not only forms the basis for maintaining host homeostasis in energy metabolism, stress response, and reproductive function but also serves as a key driver in the development of conditions such as obesity, type 2 diabetes, polycystic ovary syndrome, non-alcoholic fatty liver disease, and neuroendocrine disorders when disrupted. This article aims to systematically review the molecular and cellular mechanisms underlying major communication axes, including the gut-pancreas axis, gut-brain axis (via the HPA axis), gut-gonad axis, and gut-adipose axis. It begins by elucidating the central role of microbially derived signaling molecules (e.g., short-chain fatty acids, secondary bile acids, tryptophan metabolites) in endocrine regulation. Furthermore, the article summarizes the current status of microbiota-based diagnostic biomarkers and the potential and challenges of emerging therapeutic strategies such as fecal microbiota transplantation, precision probiotics, and microbiome engineering. Finally, it provides an outlook on future research directions, including in-depth analysis of causal relationships, development of personalized intervention strategies, and integration of the microbiota-endocrine axis into precision medicine. Understanding and modulating the dialogue between the gut microbiota and endocrine axes will offer revolutionary perspectives and novel strategies for the prevention and treatment of a range of endocrine and metabolic diseases.