女性膀胱过度活动症患者的尿液菌群特征及其与心理状态的相关性

Urinary microbiome and psychology in women with overactive bladder

目的探讨女性膀胱过度活动症（OAB）患者与健康人群的尿液菌群差异，以及OAB患者尿液菌群特征与心理状况的相关性。方法2016年11月至2017年6月我院确诊为OAB的女性患者（OAB组）和同期健康女性志愿者（对照组）纳入研究。两组均完成膀胱过度活动症症状评分表（OABSS）、焦虑自评量表（SAS）、抑郁自评量表（SDS）和生活质量评分（QOL）。通过清洁导尿收集尿液，并进行DNA提取、16SrRNA基因扩增和高通量测序。测序得到的原始数据导入QIIME软件，基于操作分类单位的分析注释结果进行样品微生物仅多样性和B多样性分析。采用LEfSe在线工具分析两组间属水平上具有显著差异的细菌，Pearson相关性分析研究心理因素评分与尿液菌群特征的关系。结果本研究OAB组和对照组分别纳人30例和25例，两组的人口学特征比较差异无明显统计学意义（P〉0．05），OAB组OABSS、SAS、SDS和QOL4个量表的得分均显著高于对照组（P〈0．01）。对照组在尿液菌群的丰富度（Chaol指数：1854．09±1239．34）和多样性（辛普森指数：0．75-4-0．23）上均显著高于OAB组（Chaol指数：2866．27±1795．22；辛普森指数：0．86±0．12；P=0．02）。门水平上，对照组拟杆菌门的相对比例（15．7％）高于OAB组（8．1％）（P=0．04）；科水平上，OAB组与对照组的肠杆菌科（17．6％与8．1％；P=0．03）和双歧杆菌科（14．8％与3．6％；P=0．01）相对比例差异有统计学意义。LEfSe分析结果显示在属水平上，OAB组和对照组尿液中分别有7个和13个菌属的相对丰度显著增加。SDS评分与香农指数（r=-0．516，P=0．003）和Chaol指数（r=-0．458，P=0．011）均呈负相关，提示OAB患者抑郁程度越重，尿液菌群的多样性和丰富度越低。结论女性OAB患者与健康女性的尿液菌群结构上存在显著差异，部分菌属可能是OAB疾病的生物标志物和潜在治疗靶点。SDS评分与OAB患者尿液菌群特征的相关性提示中枢神经系统可能与尿液菌群有关。

Objective To characterize the female urinary microbiome associated to OAB （overactive bladder） and investigate relationships between urinary microbiome and psychological factors. Methods 30 women with OAB and 25 asymptomatic controls were recruited and required to finish the overactive bladder symptom score, self-rating anxiety scale, self-rating depression scale and quality of life questionaires. Urine specimens were collected by transurethral catheterization and processed for 16S rRNA gene sequencing. Sequencing reads were processed using QIIME. Analyses for bacterial genera biomarker was used LEfSe algorithms. Bivariate correlations were assessed using Pearson＇ s correlation. Results The two cohorts showed no significance difference in their demographic characteristics. OAB patients had significantly higher scores on overactive bladder symptom score, self-rating anxiety scale, self-rating depression scale and quality of life than controls （ P 〈 0. 001 ）. We found that bacterial diversity （ Chaol index：l 854.09 ± 1 239.34） and richness （Simpson index：0.75 ±0. 23） were decreased in OAB samples than those of controls （ Chaol index ：2 866.27 ± 1 795.22 ; Simpson index ： 0.86 ± 0.12 ;P = 0.02）. At the family level, Enterobacteriaceae and （ 17.6% vs. 8.1% ; P = 0.03 ） Bifidobacteriaceae （ 14.8% vs. 3.6% ; P =0.01 ） were significantly more abundant in the OAB samples than the controls. Compared to controls,7 genera increased in OAB patients （e. g. , Proteus and Aerococcus） and 13 reduced （e. g. , Lactobacillus and Prevotella）. There are negative correlations between scores on Self-Rating Depression Scale and both Chaol （ r = - 0. 458, P = 0.011 ） and shannon indexes （ r = - 0.516, P = 0. 003 ） in OAB patients,which indicates that OAB patients with depression have further reductions in bacterial diversity and richness. Conclusions The aberrant urinary microbiome may serve as disease biomarkers and potential therapeutic targets of OAB. A negative correlation between depression scores and both bacterial richness and diversity in OAB patients indicated that there might be a connection between central nervous system and urinary microbiome.