Stern Joshua M, Moazami Saman, Qiu Yunping, Kurland Irwin, Chen Zigui, Agalliu Ilir, Burk Robert, Davies Kelvin P
Department of Urology, Albert Einstein College of Medicine, Montefiore Medical Center, Greene Medical Arts Pavilion, 5th floor, 3400 Bainbridge Avenue, Bronx, NY, 10467, USA.
Department of Medicine, Albert Einstein College of Medicine, Bronx, USA.
Urolithiasis. 2016 Oct;44(5):399-407. doi: 10.1007/s00240-016-0882-9. Epub 2016 Apr 26.
The trillions of microbes that colonize our adult intestine are referred to as the gut microbiome (GMB). Functionally it behaves as a metabolic organ that communicates with, and complements, our own human metabolic apparatus. While the relationship between the GMB and kidney stone disease (KSD) has not been investigated, dysbiosis of the GMB has been associated with diabetes, obesity and cardiovascular disease. In this pilot study we sought to identify unique changes in the GMB of kidney stone patients compared to patients without KSD. With an IRB-approved protocol we enrolled 29 patients into our pilot study. 23 patients were kidney stone formers and six were non-stone forming controls. Specimens were collected after a 6h fast and were flash frozen in dry ice and then stored at -80 °C. Microbiome: determination of bacterial abundance was by analysis of 16 s rRNA marker gene sequences using next generation sequencing. Sequencing of the GMB identified 178 bacterial genera. The five most abundant enterotypes within each group made up to greater than 50 % of the bacterial abundance identified. Bacteroides was 3.4 times more abundant in the KSD group as compared to control (34.9 vs 10.2 %; p = 0.001). Prevotella was 2.8 times more abundant in the control group as compared to the KSD group (34.7 vs 12.3 %; p = 0.005). In a multivariate analysis including age, gender, BMI, and DM, kidney stone disease remained an increased risk for high prevalence for Bacteroides (OR = 3.26, p = 0.033), whereas there was an inverse association with Prevotella (OR = 0.37, p = 0.043). There were no statistically significant differences in bacterial abundance levels for Bacteroides or Prevotella when comparing patients with and without DM, obesity (BMI >30), HTN or HLD. 11 kidney stone patients completed 24 h urine analysis at the time of this writing. Looking at the bacterial genuses with at least 4 % abundance in the kidney stone group, Eubacterium was inversely correlated with oxalate levels (r = -0.60, p < 0.06) and Escherichia trended to an inverse correlation with citrate (r = -0.56, p < 0.08). We also compared bacterial abundance between uric acid (UA) stone formers (n = 5) and non UA stone formers (n = 18) and found no significant difference between them. We identified two genus of bacteria in the GMB that had significant association with KSD. Interestingly, components of the 24-h urine appear to be correlated to bacterial abundance. These preliminary studies for the first time associate differences in the GMB with kidney stone formation. Further studies are warranted to evaluate the potential causative role of preexisting dysbiosis in kidney stone disease.
定植于我们成人肠道中的数万亿微生物被称为肠道微生物群（GMB）。在功能上，它就像一个代谢器官，与我们自身的人体代谢装置相互作用并起到补充作用。虽然尚未对GMB与肾结石疾病（KSD）之间的关系进行研究，但GMB的生态失调已与糖尿病、肥胖症和心血管疾病相关联。在这项初步研究中，我们试图确定与无KSD的患者相比，肾结石患者的GMB有哪些独特变化。根据一项经机构审查委员会（IRB）批准的方案，我们招募了29名患者进入我们的初步研究。其中23名患者是肾结石形成者，6名是无结石形成的对照者。在禁食6小时后采集样本，立即在干冰中速冻，然后储存在-80°C。微生物群：通过使用下一代测序分析16 s rRNA标记基因序列来确定细菌丰度。对GMB的测序鉴定出178个细菌属。每组中最丰富的五种肠型占所鉴定细菌丰度的50%以上。与对照组相比，KSD组中拟杆菌的丰度高3.4倍（34.9%对10.2%；p = 0.001）。与KSD组相比，对照组中普雷沃氏菌的丰度高2.8倍（34.7%对12.3%；p = 0.005）。在一项包括年龄、性别、体重指数（BMI）和糖尿病（DM）的多变量分析中，肾结石疾病仍然是拟杆菌高患病率的一个增加风险因素（比值比[OR]=3.26，p = 0.033），而与普雷沃氏菌呈负相关（OR = 0.37，p = 0.043）。在比较有和没有DM、肥胖症（BMI>30）、高血压（HTN）或高脂血症（HLD）的患者时，拟杆菌或普雷沃氏菌的细菌丰度水平没有统计学上的显著差异。在撰写本文时，11名肾结石患者完成了24小时尿液分析。观察肾结石组中丰度至少为4%的细菌属，真杆菌与草酸盐水平呈负相关（r = -0.60，p < 0.06），大肠杆菌与柠檬酸盐呈负相关趋势（r = -0.56，p < 0.08）。我们还比较了尿酸（UA）结石形成者（n = 5）和非UA结石形成者（n = 18）之间的细菌丰度，发现他们之间没有显著差异。我们在GMB中鉴定出两种与KSD有显著关联的细菌属。有趣的是，24小时尿液的成分似乎与细菌丰度相关。这些初步研究首次将GMB的差异与肾结石形成联系起来。有必要进行进一步研究以评估先前存在的生态失调在肾结石疾病中的潜在致病作用。
