肠道微生物代谢产物介导慢性肾脏病进展机制及治疗策略的研究进展

Research Progress on the Mechanisms of Gut Microbiota-Derived Metabolites Mediating the Progression of Chronic Kidney Disease and Therapeutic Strategies

摘要: 慢性肾脏病(Chronic kidney disease, CKD)已成为全球性健康危机，寻求延缓肾功能衰竭的干预靶点至关重要。“肠–肾轴”稳态失衡及其介导的代谢紊乱是CKD进展的核心病理环节。在尿毒症微环境下，肠道菌群失调产生的有害代谢物，如硫酸吲哚酚(Indoxyl sulfate, IS)、硫酸对甲酚(p-Cresyl sulfate, PCS)、氧化三甲胺(Trimethylamine N-oxide, TMAO)等，通过诱导氧化应激、炎症反应加速了肾脏纤维化进程，与此同时，短链脂肪酸(Short-chain fatty acids, SCFA)等保护性代谢物的匮乏则削弱了机体的抗炎免疫屏障。本文系统综述了上述代谢产物的分子机制，通过饮食干预、益生微生态制剂、粪菌移植及新型靶向药物重塑肠道稳态的治疗前景，旨在为CKD的临床诊疗与精准干预提供理论依据。

Abstract: Chronic kidney disease (CKD) has emerged as a global health crisis, making the search for interven-tion targets to delay renal failure of paramount importance. The homeostatic imbalance of the “gut-kidney axis” and its mediated metabolic disturbances represent core pathological links in CKD progression. Within the uremic microenvironment, deleterious metabolites generated by gut dysbiosis—such as indoxyl sulfate (IS), p-cresyl sulfate (PCS), and trimethylamine N-oxide (TMAO)—accelerate the process of renal fibrosis by inducing oxidative stress and inflammatory re-sponses. Concurrently, the deficiency of protective metabolites, such as short-chain fatty acids (SCFAs), weakens the host’s anti-inflammatory immune barrier. This article systematically reviews the molecular mechanisms of these metabolites and explores the therapeutic prospects of remod-eling intestinal homeostasis through dietary intervention, probiotic/prebiotic microecological agents, fecal microbiota transplantation, and novel targeted drugs, aiming to provide a theoretical basis for clinical diagnosis, treatment, and precision intervention in CKD.