“肠–肾轴”在肾结石形成中的作用及干预 前景

The “Gut-Kidney Axis” in Kidney Stone Formation: Mechanisms and Intervention Prospects

摘要: 肾结石病是全球最常见的泌尿系统疾病之一，患病率持续上升且复发率极高。近年来，“肠–肾轴”理论将肠道微生物群确立为肾结石形成的核心驱动因素。本文系统综述了肠道菌群通过草酸代谢、短链脂肪酸、次级胆汁酸及非结合胆红素等代谢产物调控肾结石的多通路机制。结石患者肠道菌群呈现α多样性降低、草酸降解菌减少、促炎菌属富集的特征。基于肠–肾轴的干预策略——包括靶向益生菌、合生元、粪菌移植及工程化活体生物治疗——在动物模型中展现出显著效果，但临床证据尚不充分。本文进一步深入评价了现有临床试验在样本量、菌株标准化、终点指标选择等方面的系统性设计缺陷，并据此提出了基于宏基因组数据与机器学习模型的个体化干预研究框架，以及包含草酸降解、短链脂肪酸产生和免疫调节三种功能模块的多靶点联合益生菌配方的理论设计。未来需开展大规模多组学队列研究和标准化随机对照试验，以推动肠道靶向策略的临床转化。

Abstract: Kidney stone disease is one of the most prevalent urological disorders worldwide, with a continuously rising incidence and an extremely high recurrence rate. In recent years, the “gut-kidney axis” theory has established the gut microbiota as a core driving factor in nephrolithiasis. This review systematically summarizes the multi-pathway mechanisms by which the gut microbiota regulates stone formation through oxalate metabolism, short-chain fatty acids, secondary bile acids, and unconjugated bilirubin. Stone formers characteristically exhibit reduced α-diversity, depletion of oxalate-degrading bacteria, and enrichment of pro-inflammatory genera. Gut-kidney axis-targeted interventions—including probiotics, synbiotics, fecal microbiota transplantation, and engineered live biotherapeutics—have demonstrated remarkable efficacy in animal models, yet clinical evidence remains insufficient. This article further provides an in-depth critical appraisal of the systematic design deficiencies in existing clinical trials, such as inadequate sample sizes, lack of strain standardization, and suboptimal endpoint selection. Based on this analysis, we propose a research framework for individualized intervention that integrates metagenomic data with machine learning models to predict patient-specific responses to probiotic therapies, and we present a theoretical design for a multi-target “super probiotic” formulation comprising three functional modules: oxalate degradation, short-chain fatty acid production, and immune modulation. Future large-scale multi-omics cohort studies and standardized randomized controlled trials are urgently needed to facilitate the clinical translation of gut-targeted strategies.