BACKGROUND Lower urinary tract symptoms (LUTS) is the most common complication of diabetes. However, the underlying pathogenesis of cultured negative LUTS (cn-LUTS) in diabetic patients has not been well understood. Numerous evidence indicates that urinary dysbiosis is related to urologic disorders. We aim to study alterations of the urinary microbiota of cn-LUTS in type 2 diabetes (T2D) patients. METHODS Female T2D patients and controls were recruited and requested to finish the American Urological Association Symptom Index. Mid-stream urine was collected for culturing and extracting DNA. Microbial diversity and composition were analyzed by targeting to 16S rDNA. Linear discriminant analysis effect size (LEfSe) was carried out to identify significantly different bacteria. RESULTS 32 female T2D patients and 26 controls were enrolled. No significant differences in alpha diversity were observed between patients and controls. However, statistically decreased richness (ACE index and Chao 1 index, 85.52(13.75, 204.84) vs. 129.82(63.89, 280.30) and 83.86(11.00, 210.77) vs. 125.19(62.00, 251.77), P = 0.005; Observed Species, 76(10, 175) vs. 98(54, 234), P = 0.011) and decreased species diversity (Shannon index, 1.37(0.04, 3.48) vs. 2.09(0.98, 3.43), P = 0.033; Simpson index, 0.46 (0.06, 0.99) vs. 0.23(0.07, 0.64), P = 0.029) were shown in moderate-to-severe LUTS group and high Hemoglobin A1c group, respectively. A significant difference of beta diversity was found between T2D patients and controls and T2D patients with different severity of cn-LUTS as well as the different level of Hemoglobin A1c. LEfSe revealed that 10 genera (e.g., Escherichia-Shigella and Klebsiella) were increased and 7 genera were decreasing in T2D patients, 3 genera (e.g., Escherichia-Shigella and Campylobacter) were increased and 16 genera (e.g., Prevotella) were reduced in moderate-to-severe LUTS group, 2 genera (Escherichia-Shigella and Lactobacillus) were over-represented and 10 genera (e.g., Prevotella) were under-represented in high Hemoglobin A1c group. Finally, Hemoglobin A1c was found positively correlated with the total score of the American Urological Association Symptom Index (r = 0.509, P = 0.003). CONCLUSIONS Urinary dysbiosis may be related to cn-LUTS in female T2D patients. A better understanding of urinary microbiota in the development and progression of cn-LUTS in female T2D patients was necessary. The severity of cn-LUTS was correlated to hyperglycemia and chronic hyperglycemia might induce or promote cn-LUTS by influencing urinary microbiota.

中文翻译：

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女性2型糖尿病患者尿液菌群变化与培养的下尿路阴性症状之间的关系。

背景技术下尿路症状（LUTS）是糖尿病最常见的并发症。但是，尚未充分了解糖尿病患者中培养的阴性LUTS（cn-LUTS）的潜在发病机理。大量证据表明，泌尿系统疾病与泌尿系统疾病有关。我们旨在研究2型糖尿病（T2D）患者中cn-LUTS尿液微生物群的变化。方法招募女性T2D患者和对照组，并要求他们完成美国泌尿外科协会症状指数。收集中游尿液用于培养和提取DNA。通过靶向16S rDNA分析微生物的多样性和组成。进行线性判别分析效果大小（LEfSe）以鉴定明显不同的细菌。结果招募了32例女性T2D患者和26例对照组。患者和对照之间没有观察到阿尔法多样性的显着差异。但是，统计上的丰富度下降（ACE指数和Chao 1指数，85.52（13.75，204.84）对129.82（63.89，280.30）和83.86（11.00，210.77）对125.19（62.00，251.77），P = 0.005; 76（10，175）对98（54，234），P = 0.011）和物种多样性降低（香农指数，1.37（0.04，3.48）对2.09（0.98，3.43），P = 0.033;辛普森指数，0.46中重度LUTS组和高血红蛋白A1c组分别显示（0.06，0.99）vs.0.23（0.07，0.64），P = 0.029）。发现T2D患者和对照组以及具有不同cn-LUTS严重程度以及不同水平的血红蛋白A1c的T2D患者之间的β多样性存在显着差异。LEfSe揭示了10个属（例如，在中至重度LUTS组中，T2D患者的Escherichia-Shigella和Klebsiella升高了7属，降低了3属（例如Escherichia-Shigella和弯曲杆菌），减少了16属（例如Prevotella），2高血红蛋白A1c组中Escherichia-Shigella和Lactobacillus属超过10个属（如Prevotella）。最后，发现血红蛋白A1c与美国泌尿科协会症状指数的总得分呈正相关（r = 0.509，P = 0.003）。结论女性T2D患者尿毒症可能与cn-LUTS有关。有必要更好地了解女性T2D患者cn-LUTS的发展和进程中的尿菌群。