Department of Urology, General Hospital of Central Theater Command of Chinese People's Liberation Army, Wuhan, Hubei, China.
The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
Front Cell Infect Microbiol. 2023 May 29;13:1145196. doi: 10.3389/fcimb.2023.1145196. eCollection 2023.
The incidence of nephrolithiasis is increasing rapidly worldwide. Calcium oxalate is the most common constituent, contributing to approximately 80% of all kidney stones. The gut microbiome, through its oxalate-degrading ability, may play a role in decreasing morbidity due to urinary calculus. Fecal microbiome transplantation (FMT) has been reported to be effective in restoring the gastrointestinal microbial community in different conditions. The transplantation of whole communities that have oxalate-degrading function may be a more effective strategy than the transplantation of isolated strains.
FMT was carried out in male guinea pigs and male Sprague-Dawley laboratory rats (SDRs). Fresh feces were collected from guinea pigs housed in metabolic cages. SDRs were divided into four groups: two groups received standard rat chow (SC) (groups SC and SC + FMT), and two groups were fed a 5% potassium oxalate diet (OD) (groups OD + phosphate-buffered saline (PBS) and OD + FMT). On day 14, groups OD + PBS, OD + FMT, and SC + FMT received either PBS or guinea pig feces by esophageal gavage. The composition of the microbiota of guinea pigs and SDRs was analyzed using a 16S rRNA gene sequencing approach. Biochemical analysis of urine samples from SDRs revealed the presence of calcium oxalate (CaOx) crystals, which were presumed to originate from kidney stones. Renal function was examined using real-time PCR analysis and immunohistochemical staining for renin, angiotensin-converting enzyme, and osteopontin (OPN) expression.
FMT resulted in a gut microbiota that was a mixture of guinea pig and SDR bacteria. A microbial network involving Muribaculaceae, , and was activated by FMT in group OD + FMT. As a result, urinary oxalate, calcium, uric acid, creatinine and urea in urine samples were reduced significantly. Similarly, significant reduction of uric acid and blood urea nitrogen to creatinine ratio in serum samples was observed ( < 0.05). Microscopic observations revealed a high CaOx crystal score (4+) in the kidneys of rats in group OD + PBS, whereas a lower score (2+) was observed in the rats in group OD + FMT. Up-regulation of OPN and down-regulation of renin were also associated with FMT.
A microbial network involving Muribaculaceae and other oxalate-degrading bacteria achieved by FMT was capable of reducing urinary oxalate excretion and CaOx crystal deposition in the kidney through increasing intestinal oxalate degradation. FMT may exert a renoprotective function in oxalate-related kidney stones.
肾结石的发病率在全球范围内迅速上升。草酸钙是最常见的成分，约占所有肾结石的 80%。肠道微生物组通过其降解草酸的能力，可能在降低尿路结石的发病率方面发挥作用。粪菌移植（FMT）已被报道在恢复不同条件下的胃肠道微生物群落方面是有效的。移植具有降解草酸功能的整个群落可能比移植分离株更有效。
在雄性豚鼠和雄性 Sprague-Dawley 实验室大鼠（SDR）中进行 FMT。从饲养在代谢笼中的豚鼠中收集新鲜粪便。SDR 分为四组：两组给予标准大鼠饲料（SC）（SC 组和 SC+FMT 组），两组给予 5%草酸钾饮食（OD）（OD+磷酸盐缓冲盐水（PBS）组和 OD+FMT 组）。第 14 天，OD+PBS、OD+FMT 和 SC+FMT 组通过食管灌胃分别给予 PBS 或豚鼠粪便。使用 16S rRNA 基因测序方法分析豚鼠和 SDR 微生物群的组成。SDR 尿液样本的生化分析显示存在草酸钙（CaOx）晶体，推测这些晶体源自肾结石。使用实时 PCR 分析和肾素、血管紧张素转换酶和骨桥蛋白（OPN）表达的免疫组织化学染色检查肾功能。
FMT 导致肠道微生物群是豚鼠和 SDR 细菌的混合物。FMT 在 OD+FMT 组中激活了涉及 Muribaculaceae、和的微生物网络。结果，尿液样本中的尿草酸、钙、尿酸、肌酐和尿素显著减少。同样，血清样本中的尿酸和血尿素氮与肌酐比值也观察到显著降低（<0.05）。显微镜观察显示，OD+PBS 组大鼠肾脏的 CaOx 晶体评分（4+）较高，而 OD+FMT 组大鼠的评分（2+）较低。FMT 还与 OPN 的上调和肾素的下调相关。
FMT 形成的涉及 Muribaculaceae 和其他降解草酸细菌的微生物网络能够通过增加肠道草酸降解来减少尿草酸排泄和肾脏中 CaOx 晶体沉积。FMT 可能在草酸相关肾结石中发挥肾脏保护作用。
