Male urethritis: Novel etiologies and natural history

描述(申请人提供)：尿道炎是最常见的男性生殖道综合征，但高达50%的病例没有已知的病因。最近，我们发现对女性细菌性阴道病(BV)高度敏感和特异的新发现细菌Leptotricia/Sneathia spp.与男性特发性尿道炎显著相关。 另外两种新描述的细菌(BV相关细菌[BVAB]2和BVAB3)在特发性尿道炎患者中发现的频率比对照组男性更高，这表明这三种细菌都可能在尿道炎中发挥作用。此外，特发性尿道炎患者的尿路微生物群落与健康男性不同，而且尿道炎患者体内乳杆菌的相对丰度一直较高，这表明尿道炎患者尿路微生物区系的变化也可能在尿道炎的发展中起到因果作用。考虑到男性尿道炎相对常见的性质，其复发的倾向，以及原因不明病例的高比例，我们提出了一个两级策略来确定这种疾病的新病因。在物种特异性的方法中，我们将使用物种特异性定量聚合酶链式反应(Leptotricia/Sneathia spp.，BVAB2，BVAB3)来前瞻性地评估3种新描述的细菌与尿道炎的发病率、消退和复发的关系。在元基因组学方法中，我们将使用广泛的16S rRNA基因聚合酶链式反应和焦磷酸测序来描述随着时间的推移男性尿路细菌生物群，并评估微生物群落中细菌的种类组成和/或特定细菌(L.iners等)的相对丰度的变化是否与尿道炎的发病率、消退和复发有关。最后，我们假设这些细菌和细菌群落是性传播的，并将评估性接触、获得3种新描述的细菌和/或微生物群落中的任何一种和新出现的尿道炎临床体征和症状之间的关系。这些研究将加强男性尿道炎的临床治疗，并可能导致新的诊断工具、治疗方法和预防策略的开发。考虑到大多数生殖道细菌的性传播性质，平行的好处 对于女性生殖道疾病的临床处理可能随之而来。

DESCRIPTION (provided by applicant): Urethritis is the most common male reproductive tract syndrome, yet up to 50% of cases have no known etiology. Recently, we found that Leptotrichia/Sneathia spp., newly described bacteria that are highly sensitive and specific for bacterial vaginosis (BV) in women, were significantly associated with idiopathic urethritis in men. Two other newly described bacteria (BV-associated bacterium [BVAB] 2, and BVAB3) were found more often in men with idiopathic urethritis than in control men, suggesting that all 3 of these bacteria may play a role in urethritis. Furthermore, men with idiopathic urethritis had urethral microbial communities that were distinct from those in healthy men, and relative abundance of Lactobacillis iners was consistently higher in men with urethritis, suggesting that changes in the urethral microbiota may also play a causal role in the development of urethritis. Given the relatively common nature of male urethritis, its propensity to recur, and the high proportion of unexplained cases, we propose a 2-tiered strategy to identify novel etiologies of this condition. In a species-specific approach, we will prospectively assess the relationship between 3 newly described bacteria (Leptotrichia/Sneathia spp., BVAB2, BVAB3) and the incidence, resolution and recurrence of urethritis using species-specific quantitative PCR. In a metagenomic approach, we will use broad range 16S rRNA gene PCR with pyrosequencing to describe the urethral bacterial biota in men over time and to assess whether changes in species composition of bacteria in microbial communities and/or relative abundance of specific bacteria (L. iners, among others) are associated with incidence, resolution and recurrence of urethritis. Finally, we hypothesize that these bacteria and bacterial communities are sexually transmitted and will assess the relationships between specific sexual exposures, acquisition of any of the 3 newly described bacteria and/or changes in microbial communities, and new onset of clinical signs and symptoms of urethritis. These studies will enhance the clinical management of male urethritis, and may lead to the development of new diagnostic tools, therapies and prevention strategies. Given the sexually transmitted nature of most genital tract bacteria, parallel benefits for clinical management of female reproductive tract disease may follow.