Shrestha Eva, White James R, Yu Shu-Han, Kulac Ibrahim, Ertunc Onur, De Marzo Angelo M, Yegnasubramanian Srinivasan, Mangold Leslie A, Partin Alan W, Sfanos Karen S
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Resphera Biosciences, Baltimore, Maryland.
J Urol. 2018 Jan;199(1):161-171. doi: 10.1016/j.juro.2017.08.001. Epub 2017 Aug 7.
Studies demonstrating bacterial DNA and cultivable bacteria in urine samples have challenged the clinical dogma that urine is sterile. Furthermore, studies now indicate that dysbiosis of the urinary microbiome is associated with pathological conditions. We propose that the urinary microbiome may influence chronic inflammation observed in the prostate, leading to prostate cancer development and progression. Therefore, we profiled the urinary microbiome in men with positive vs negative biopsies for prostate cancer.
Urine was collected from men prior to biopsy for prostate cancer. DNA was extracted from urine pellet samples and subjected to bacterial 16S rDNA Illumina® sequencing and 16S rDNA quantitative polymerase chain reaction. We determined the association between bacterial species and the presence or absence of cancer, cancer grade, and type and degree of prostate inflammation.
Urine samples revealed diverse bacterial populations. There were no significant differences in α or β diversity and no clear hierarchical clustering of benign or cancer samples. We identified a cluster of pro-inflammatory bacteria previously implicated in urogenital infections in a subset of samples. Many species, including known uropathogens, were significantly and differentially abundant among cancer and benign samples, in low vs higher grade cancers and in relation to prostate inflammation type and degree.
To our knowledge we report the most comprehensive study to date of the male urinary microbiome and its relationship to prostate cancer. Our results suggest a prevalence of pro-inflammatory bacteria and uropathogens in the urinary tract of men with prostate cancer.
多项研究表明尿液样本中存在细菌DNA和可培养细菌，这对尿液是无菌的临床教条提出了挑战。此外，现在有研究表明泌尿微生物群失调与病理状况有关。我们提出泌尿微生物群可能会影响前列腺中观察到的慢性炎症，从而导致前列腺癌的发生和进展。因此，我们对前列腺癌活检呈阳性和阴性的男性的泌尿微生物群进行了分析。
在对男性进行前列腺癌活检之前收集尿液。从尿沉渣样本中提取DNA，并进行细菌16S rDNA Illumina®测序和16S rDNA定量聚合酶链反应。我们确定了细菌种类与癌症的有无、癌症分级以及前列腺炎症的类型和程度之间的关联。
尿液样本显示出多样的细菌种群。α或β多样性没有显著差异，良性或癌症样本也没有明显的层次聚类。我们在一部分样本中发现了一组先前与泌尿生殖系统感染有关的促炎细菌。许多种类，包括已知的尿路病原体，在癌症样本和良性样本之间、低级别与高级别癌症之间以及与前列腺炎症类型和程度相关的样本中，丰度存在显著差异。
据我们所知，我们报告了迄今为止关于男性泌尿微生物群及其与前列腺癌关系的最全面研究。我们的结果表明，前列腺癌男性的尿路中存在促炎细菌和尿路病原体。
