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中华临床医师杂志(电子版) ›› 2026, Vol. 20 ›› Issue (05) : 351 -360. doi: 10.3877/cma.j.issn.1674-0785.2026.05.003

临床研究

草酸钙尿路结石患者肠道菌群结构与靶向代谢谱的关联特征研究
张天民1,2, 颜尧2, 张先云1, 吴自余1, 王苏贵1,(), 姜福金1,()   
  1. 1 223002 江苏淮安,徐州医科大学附属淮安医院泌尿外科
    2 223300 江苏淮安,扬州大学附属淮安医院(淮安市第五人民医院)泌尿外科
  • 收稿日期:2026-04-28 出版日期:2026-05-30
  • 通信作者: 王苏贵, 姜福金
  • 基金资助:
    江苏省第十六批“六大人才高峰”项目资助(WSW-218)

Correlation of gut microbiota structure with targeted metabolome in patients with calcium oxalate urolithiasis

Tianmin Zhang1,2, Yao Yan2, Xianyun Zhang1, Ziyu Wu1, Sugui Wang1,(), Fujin Jiang1,()   

  1. 1 Department of Urology, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an 223002, China
    2 Department of Urology, Huai'an Hospital Affiliated to Yangzhou University (The Fifth People's Hospital of Huai'an), Huai'an 223300, China
  • Received:2026-04-28 Published:2026-05-30
  • Corresponding author: Sugui Wang, Fujin Jiang
引用本文:

张天民, 颜尧, 张先云, 吴自余, 王苏贵, 姜福金. 草酸钙尿路结石患者肠道菌群结构与靶向代谢谱的关联特征研究[J/OL]. 中华临床医师杂志(电子版), 2026, 20(05): 351-360.

Tianmin Zhang, Yao Yan, Xianyun Zhang, Ziyu Wu, Sugui Wang, Fujin Jiang. Correlation of gut microbiota structure with targeted metabolome in patients with calcium oxalate urolithiasis[J/OL]. Chinese Journal of Clinicians(Electronic Edition), 2026, 20(05): 351-360.

目的

基于肠道菌群与血清代谢组学的联合分析,探讨草酸钙尿路结石患者的肠道菌群结构特征及其与代谢谱变化之间的关联机制。

方法

选取经影像学确诊的草酸钙尿路结石患者及健康对照者,采集粪便及空腹血清样本。采用16S rRNA高通量测序分析肠道菌群结构,采用UHPLC-MS/MS进行靶向代谢组学检测。多变量统计分析筛选差异菌群及代谢物,Spearman相关性分析构建菌群-代谢物关联网络。

结果

与健康对照组相比,草酸钙结石患者肠道菌群物种丰富度升高,菌群结构明显分离。菌群组成方面,共生菌如双歧杆菌属、布劳特氏菌属及罗斯氏菌属显著减少,而拟杆菌属、普雷沃菌属及阿克曼菌属相对增加。代谢组学结果显示患者血清代谢谱显著改变,主要表现为脂质代谢紊乱、氨基酸代谢异常及氧化应激相关代谢物下降。相关性分析提示肠道菌群与多种代谢物之间存在显著相关性。

结论

草酸钙尿路结石患者存在肠道菌群结构失衡及血清代谢谱紊乱,二者通过多通路相互作用共同参与疾病发生过程。

Objective

To investigate the structural characteristics of gut microbiota in patients with calcium oxalate urinary calculi and to explore the correlation mechanisms underlying serum metabolic, based on an integrated analysis of gut microbiomics and serum metabolomics.

Methods

Patients with imaging-confirmed calcium oxalate urinary calculi and healthy controls were enrolled. Fecal samples and fasting serum specimens were collected from all participants. 16S rRNA high-throughput sequencing was applied to analyze gut microbiota structure, and UHPLC-MS/MS was used for targeted metabolomics profiling. Multivariate statistical analyses were performed to identify differentially abundant microbial taxa and metabolites. Spearman correlation analysis was adopted to construct the microbiota-metabolite correlation network.

Results

Compared with the healthy control group, patients with calcium oxalate calculi presented increased species richness of gut microbiota and significantly distinct microbial community structure. In terms of microbial composition, symbiotic bacteria including Bifidobacterium, Blautia, and Roseburia were markedly decreased, while the relative abundances of Bacteroides, Prevotella, and Akkermansia were increased. Metabolomic results indicated obvious disturbances in serum metabolic profiles of patients, which were predominantly characterized by lipid metabolism disorders, abnormal amino acid metabolism, and reduced levels of oxidative stress-related metabolites. Correlation analysis revealed significant correlations between specific gut microbial taxa and multiple differentially expressed metabolites.

Conclusion

Patients with calcium oxalate urinary calculi exhibit gut microbiota dysbiosis and disrupted serum metabolic profiles. These two layers of alteration may interact through multiple interconnected pathways and jointly contribute to the pathogenesis of the disease.

表1 草酸钙尿路结石患者临床基本信息及围手术期指标
图1 健康对照组与草酸钙结石患者肠道菌群多样性分析。图a为健康对照组(Healthy,绿色)与草酸钙结石观察组(Patients,紫色)肠道菌群Alpha多样性指数箱线图;图b为Beta多样性PCA分析
图2 2组受试者肠道菌群组成与差异物种分析。图a为门水平(Top20)菌群相对丰度堆叠图;图b为属水平(Top20)菌群相对丰度堆叠图;图c为LEfSe差异物种分析;图d为ASV韦恩图;图e为组间差异菌门/菌属相对丰度堆叠图
图3 2组受试者血清代谢组学多变量统计分析注。图a为PCA得分图;图b为OPLS-DA得分图;图c为OPLS-DA置换检验图(R2Y=0.9962,Q2=0.25);图d为火山图(以VIP>1、P<0.05、|log2FC|>1为标准筛选差异代谢物,红色为上调代谢物,蓝色为下调代谢物,灰色为无显著差异代谢物)
表2 健康对照组与草酸钙结石患者组的20种差异代谢物
图4 肠道菌群与血清差异代谢物的Spearman相关性分析。图a为Spearman相关系数分布直方图;图b为关键菌属与差异代谢物相关性热图,aP<0.05,bP<0.01,cP<0.001;图c为全菌群-代谢物相关性三角热图
1
Zheng J, Zhang J, Cai J, et al. Development of a radiomics model to discriminate ammonium urate stones from uric acid stones in vivo : a remedy for the diagnostic pitfall of dual-energy computed tomography [J]. Chin Med J (Engl), 2024, 137(9): 1095-1104.
2
袁晓亮, 魏汉平, 刘晓武, 等. 泌尿系结石成分构成及其临床特征与肾功能分析 [J]. 中外医学研究, 2022, 20(22): 68-72.
3
Aji K, Maimaijiang M, Song G. Study on changes in urinary relative supersaturation and risk of stone recurrence in patients after urolithiasis surgery [J]. BMC Urol, 2025, 25(1): 258.
4
阮星星, 刘芙香, 周祥福. 欧洲泌尿外科学会尿路结石诊断与治疗指南要点 [J/OL]. 中华腔镜泌尿外科杂志(电子版), 2025, 19(6): 758.
5
岑威虎, 沈俊, 夏莎莎, 等. 代谢相关疾病与草酸钙结石形成机制的研究进展 [J]. 中国医学科学院学报, 2025, 47(1): 124-130.
6
Gao J, Xue JF, Xu M, et al. Nanouric acid or nanocalcium phosphate as central nidus to induce calcium oxalate stone formation: a high-resolution transmission electron microscopy study on urinary nanocrystallites [J]. Int J Nanomedicine, 2014, 9: 4399-4409.
7
Origüela V, Lopez-Zaplana A. Gut microbiota: an immersion in dysbiosis, associated pathologies, and probiotics [J]. Microorganisms, 2025, 13(5): 1084.
8
王超, 董旭, 尹新玮, 等. 肠道菌群对草酸钙结石的影响 [J]. 中南大学学报(医学版), 2021, 46(11): 1285-1289.
9
Kim MG, Yang J, Jo SK. Intestinal microbiota and kidney diseases [J]. Kidney Res Clin Pract, 2021, 40(3): 335-343.
10
方道成, 唐春华, 胡媛媛. 肠道菌群对草酸钙肾结石形成的影响 [J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(5): 509-513.
11
刘志楠, 徐卫波, 刘博文, 等. 泌尿系结石与肠道微生态关系研究进展 [J]. 临床泌尿外科杂志, 2022, 37(2): 156-159, 162.
12
Mehta M, Goldfarb DS, Nazzal L. The role of the microbiome in kidney stone formation [J]. Int J Surg, 2016, 36(Pt D): 607-612.
13
何春燕, 张宁南, 杨敏, 等. 肠道与泌尿系统的微生物对肾结石发病机制影响的研究进展 [J]. 微生物学通报, 2022, 49(9): 3967-3978.
14
Li D, Li Z, Liu W. The gut-kidney axis in urolithiasis: roles of gut microbiota, metabolites, and therapeutic implications [J]. Front Microbiol, 2025, 16: 1655808.
15
蒋兆彦, 胡海, 韩天权, 等. 肠道菌群改变与胆固醇结石病 [J]. 外科理论与实践, 2019, 24(2): 93-95.
16
Ticinesi A, Nouvenne A, Chiussi G, et al. Calcium oxalate nephrolithiasis and gut microbiota: not just a gut-kidney axis. A nutritional perspective [J]. Nutrients, 2020, 12(2): 548.
17
Chen X, Zhang F, Cheng L, et al. Dysbiosis of the gut microbiota in calcium oxalate nephrolithiasis is associated with impaired short-chain fatty acid production and systemic metabolomic disruptions [J]. Microbiome, 2025, 14(1): 35.
18
Sadaf H, Raza SI, Hassan SW. Role of gut microbiota against calcium oxalate [J]. Microb Pathog, 2017, 109: 287-291.
19
任向楠, 梁琼麟. 基于质谱分析的代谢组学研究进展 [J]. 分析测试学报, 2017, 36(2): 161-169.
20
Cui T, Yang Y, Lange D, et al. Gut microbiome and metabolome signatures in calcium oxalate stone recurrence: a multi-omics study [J]. Microb Cell Fact, 2026, 25(1): 100.
21
Stanford J, Charlton K, Stefoska-Needham A, et al. The gut microbiota profile of adults with kidney disease and kidney stones: a systematic review of the literature [J]. BMC Nephrol, 2020, 21(1): 215.
22
Yuan T, Xia Y, Li B, et al. Gut microbiota in patients with kidney stones: a systematic review and meta-analysis [J]. BMC Microbiol, 2023, 23(1): 143.
23
Li XM, Amier Y, Wan WL, et al. A novel synbiotic formulation prevents calcium oxalate stones by restoring gut microbiota homeostasis [J]. BMC Microbiol, 2025, 25(1): 673.
24
Ma J, Piao X, Mahfuz S, et al. The interaction among gut microbes, the intestinal barrier and short chain fatty acids [J]. Anim Nutr, 2021, 9: 159-174.
25
Margolis KG, Cryan JF, Mayer EA. The microbiota-gut-brain axis: From motility to mood [J]. Gastroenterology, 2021, 160(5): 1486-1501.
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