Jing Junfeng, Yan Xu, Wang Lang, Zhang Yanbin, Qi Wei, Xi Junhua, Hao Zongyao
Department of Urology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical University, 230022, Hefei, Anhui, China.
Department of Urology, The Second People's Hospital of Hefei, Hefei Hospital, Affiliated to Anhui Medical University, Hefei, 230011, China.
Urolithiasis. 2025 Jul 2;53(1):134. doi: 10.1007/s00240-025-01779-0.
The exact mechanism of calcium oxalate stone (CaOx) formation is not fully understood. Evidence suggests that disruptions in the gut microbiota and its metabolites influence kidney stone formation. We conducted microbiome-metabolome analysis to pinpoint microbial metabolites linked to kidney stones in both patient and healthy control groups. We explored the impact of these kidney stone-related microbial metabolites on CaOx-induced stones, along with their underlying mechanisms of action. We exposed NRK-52E cells to CaOx crystals that had been pretreated with indole-3-acetic acid. Rats, induced to develop CaOx stones via ethylene glycol and ammonium chloride administration, were also treated with IAA. Our investigations encompassed assessments of Ca levels, reactive oxygen species levels, markers of oxidative stress, apoptosis levels, inflammation levels, and gene expression within AHR/NF‑κB pathway, both in cellular and tissue samples.Indole-3-acetic acid showed significantly reduction in patients with renal stones. The administration of IAA has been found to alleviate the deposition and adhesion of calcium oxide stones in the kidneys. Furthermore, IAA demonstrates beneficial effects on kidney damage and inflammation. IAA efficiently reduces intracellular levels of ROS, osteopontin, and CD44 in NRK-52E cells exposed to CaOx as well as in a rat model of stone formation. Mechanistically, IAA inhibits the activation of the NF-κB signaling pathway through the elevation of AHR in kidney stones. Our research has uncovered a novel connection between gut microbiota-derived tryptophan metabolites and kidney stones. The microbial metabolite IAA/AHR/NF-κB pathway may be a promising target for kidney stone treatment.
草酸钙结石（CaOx）形成的确切机制尚未完全明确。有证据表明，肠道微生物群及其代谢产物的紊乱会影响肾结石的形成。我们进行了微生物组-代谢组分析，以确定患者组和健康对照组中与肾结石相关的微生物代谢产物。我们探讨了这些与肾结石相关的微生物代谢产物对草酸钙诱导结石的影响及其潜在作用机制。我们将NRK-52E细胞暴露于用吲哚-3-乙酸预处理过的草酸钙晶体中。通过给予乙二醇和氯化铵诱导形成草酸钙结石的大鼠也用吲哚-3-乙酸进行了处理。我们的研究包括对细胞和组织样本中的钙水平、活性氧水平、氧化应激标志物、凋亡水平、炎症水平以及芳香烃受体/核因子-κB（AHR/NF-κB）途径中的基因表达进行评估。吲哚-3-乙酸在肾结石患者中显著减少。已发现给予吲哚-3-乙酸可减轻肾脏中氧化钙结石的沉积和黏附。此外，吲哚-3-乙酸对肾脏损伤和炎症具有有益作用。吲哚-3-乙酸能有效降低暴露于草酸钙的NRK-52E细胞以及结石形成大鼠模型中的细胞内活性氧、骨桥蛋白和CD44水平。从机制上讲，吲哚-3-乙酸通过提高肾结石中芳香烃受体的水平来抑制核因子-κB信号通路的激活。我们的研究发现了肠道微生物群衍生的色氨酸代谢产物与肾结石之间的新联系。微生物代谢产物吲哚-3-乙酸/芳香烃受体/核因子-κB途径可能是肾结石治疗的一个有前景的靶点。
