Zhou Yuhao, Lei Min, Cai Weihong, Chang Zhenglin, An Lingyue, Zhang Shike, Wei Daqiang, Jiao Renjie, Gao Jie, Xu Yangzhi, Yang Hui, Zhu Mingzhao, Cao Jiabao, Li Shujue, Duan Xiaolu, Wu Wenqi
Department of Urology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
mSystems. 2025 Aug 25:e0081025. doi: 10.1128/msystems.00810-25.
High dietary oxalate (HDOx) diet is a key factor in kidney stone formation, with gut microbiota playing a significant role. Although several studies have indicated that fecal microbiota transplantation from healthy animals can effectively reduce renal calcium oxalate (CaOx) depositions in rats, the gut microbiota composition between human and animal still remains different. This study aims to explore the effect and underlying mechanisms of healthy human-source fecal microbiota transplantation (hFMT) on CaOx crystal depositions, providing new evidence for its potential clinical application in hyperoxaluria and kidney stone treatment. First, fecal microbiota were screened and collected from healthy individuals and transplanted into rats fed with hydroxyproline. We found that hFMT effectively inhibited crystal depositions and kidney injury induced by HDOx diet, regardless of antibiotic pretreatment. Additionally, 16S rDNA sequencing of gut microbiota identified that hFMT treatment reversed HDOx-induced gut microbiota composition change, particularly restoring the abundance and ecological network of , which was a key indicator genus associated with CaOx crystal depositions. Compared to controls, the abundance of was increased in fecal samples from kidney stone patients and another rat model fed with potassium oxalate. Mechanistically, hFMT markedly attenuated HDOx-induced intestinal barrier disruption to reverse the formation of CaOx crystallization. These findings suggest that HDOx diets could significantly influence the rat gut microbiota. hFMT effectively reduces HDOx-induced renal CaOx crystal depositions and kidney injury via repairing -related gut barrier damage in rats. These findings underscore the potential of hFMT as a therapeutic strategy for hyperoxaluria and kidney stone treatment.
This study investigated that healthy hFMT could serve as a novel strategy to inhibit kidney CaOx deposition induced by HDOx diet. By transplanting healthy human gut microbiota into HDOx rats, we found that hFMT significantly reduced CaOx crystal depositions and kidney damage. The treatment also restored the gut microbiota composition, particularly the abundance of , a genus closely associated with CaOx crystal depositions. Importantly, hFMT restored intestinal barrier function, providing a new mechanistic insight into the gut-kidney axis in kidney stone formation. These findings highlight hFMT's potential as a therapeutic strategy for managing hyperoxaluria and kidney stone, offering a promising alternative to traditional treatment.
高膳食草酸盐（HDOx）饮食是肾结石形成的关键因素，肠道微生物群起着重要作用。尽管多项研究表明，来自健康动物的粪便微生物群移植可有效减少大鼠肾草酸钙（CaOx）沉积，但人与动物之间的肠道微生物群组成仍存在差异。本研究旨在探讨健康人源粪便微生物群移植（hFMT）对CaOx晶体沉积的影响及潜在机制，为其在高草酸尿症和肾结石治疗中的潜在临床应用提供新证据。首先，从健康个体中筛选并收集粪便微生物群，移植到喂食羟脯氨酸的大鼠体内。我们发现，无论是否进行抗生素预处理，hFMT均能有效抑制HDOx饮食诱导的晶体沉积和肾损伤。此外，肠道微生物群的16S rDNA测序表明，hFMT治疗逆转了HDOx诱导的肠道微生物群组成变化，特别是恢复了与CaOx晶体沉积相关的关键指示菌属的丰度和生态网络。与对照组相比，肾结石患者和另一个喂食草酸钾的大鼠模型的粪便样本中该菌属的丰度增加。从机制上讲，hFMT显著减轻了HDOx诱导的肠道屏障破坏，从而逆转了CaOx结晶的形成。这些发现表明，HDOx饮食可显著影响大鼠肠道微生物群。hFMT通过修复大鼠中与该菌属相关的肠道屏障损伤，有效减少了HDOx诱导的肾CaOx晶体沉积和肾损伤。这些发现强调了hFMT作为高草酸尿症和肾结石治疗策略的潜力。
本研究调查发现，健康的hFMT可作为一种新型策略来抑制HDOx饮食诱导的肾CaOx沉积。通过将健康人肠道微生物群移植到HDOx大鼠体内，我们发现hFMT显著减少了CaOx晶体沉积和肾损伤。该治疗还恢复了肠道微生物群组成，特别是与CaOx晶体沉积密切相关的菌属的丰度。重要的是，hFMT恢复了肠道屏障功能，为肾结石形成中的肠-肾轴提供了新的机制见解。这些发现突出了hFMT作为治疗高草酸尿症和肾结石的治疗策略的潜力，为传统治疗提供了有希望的替代方案。
