精神分裂症代谢综合征与肠道菌群的研究进展

Research Advances in Metabolic Syndrome and Gut Microbiota in Schizophrenia

摘要: 精神分裂症(Schizophrenia, SCZ)患者代谢综合征(Metabolic Syndrome, MetS)的发生率显著高于普通人群，另外这一共病现象还是导致患者预期寿命缩短的主要原因。已有研究表明，SCZ与MetS在病理及生物学基础上面存在共同的机制，比如促炎因子中的白细胞介素6及TNF-α水平升高，通过激活核因子κB通路促进胰岛素抵抗及脂质代谢紊乱。神经内分泌异常使下丘脑–垂体–肾上腺轴过度激活，导致皮质醇水平升高，从而加剧腹型肥胖及糖代谢异常。第二代抗精神病药物通过拮抗5-羟色胺2C受体及组胺受体，增加食欲并抑制能量消耗。随着多组学技术的飞速发展，肠道菌群在联接精神症状与代谢紊乱的枢纽中起着关键的作用，如果菌群失衡，患者肠道内厚壁菌门/拟杆菌门比值会升高，产短链脂肪酸(Short-Chain Fatty Acids, SCFAs)菌丰度会降低，最终导致肠道屏障完整性破坏及内毒素入血，触发代谢性炎症；SCFAs通过激活G蛋白偶联受体GPR43/41受体调节糖脂代谢，色氨酸代谢紊乱可能加剧胰岛素抵抗及氧化应激。本文综述了肠道菌群在SCZ患者MetS中的最新研究进展，重点探讨了肠道菌群失衡与免疫功能异常之间的联系及其对代谢状态的影响，此外，还总结了当前基于肠道菌群的潜在干预策略，为未来精准治疗提供理论依据和研究方向。

Abstract: Patients with schizophrenia (SCZ) have a significantly higher prevalence of metabolic syndrome (MetS) than the general population, and this comorbidity is a major factor leading to shortened life expectancy. Studies have shown that SCZ and MetS share similar pathological and biological mechanisms. Increased levels of interleukin-6 (IL-6) and TNF-α can activate the NF-κB pathway and induce insulin resistance and lipid metabolism disorders. Overactivation of the hypothalamic-pituitary-adrenal (HPA) axis due to neuroendocrine dysfunction elevates cortisol levels, aggravating abdominal obesity and abnormal glucose metabolism. Second-generation antipsychotics (SGAs) increase appetite and reduce energy expenditure by blocking 5-HT₂C and histamine receptors. With the development of multi-omics technologies, gut microbiota plays a key role in linking psychiatric symptoms and metabolic disorders. Gut dysbiosis leads to an elevated Firmicutes/Bacteroidetes ratio and decreased abundance of SCFA-producing bacteria, which damages intestinal barrier integrity, causes endotoxin translocation and triggers metabolic inflammation. SCFAs regulate glucose and lipid metabolism via GPR41/GPR43, and abnormal tryptophan metabolism may worsen insulin resistance and oxidative stress. This article reviews recent advances in gut microbiota research on MetS in SCZ patients, discusses the relationship between gut dysbiosis and immune dysfunction, and summarizes potential microbiota-based interventions, so as to provide theoretical support and new directions for future precision treatment.