Male urethritis: Novel etiologies and natural history

描述（由申请人提供）：尿道炎是最常见的男性生殖道综合征，但高达50%的病例病因不明。最近，我们发现Leptotrichia/Sneathia spp.，一种新发现的对女性细菌性阴道病（BV）高度敏感和特异的细菌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BVAB 3）在患有特发性尿道炎的男性中比对照男性更常见，这表明所有3种细菌都可能在尿道炎中发挥作用。此外，患有特发性尿道炎的男性具有与健康男性不同的尿道微生物群落，并且尿道炎男性中的乳酸杆菌的相对丰度始终较高，这表明尿道微生物群的变化也可能在尿道炎的发展中发挥因果作用。鉴于男性尿道炎相对常见的性质，其复发的倾向，以及不明原因的病例比例高，我们提出了一个2层的策略，以确定这种情况下的新病因。我们将采用种属特异性方法，前瞻性评估3种新描述的细菌（Leptotrichia/Sneathia spp.，BVAB 2，BVAB 3）和尿道炎的发病率，解决和复发使用物种特异性定量PCR。在宏基因组学方法中，我们将使用广泛的16 S rRNA基因PCR和焦磷酸测序来描述男性尿道细菌生物群随时间的变化，并评估微生物群落中细菌的物种组成和/或特定细菌（L.尤其是Iners）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，并将评估特定的性暴露，3种新描述的细菌和/或微生物群落变化中的任何一种的获得，以及尿道炎临床体征和症状的新发之间的关系。这些研究将加强男性尿道炎的临床管理，并可能导致新的诊断工具，治疗和预防策略的发展。鉴于大多数生殖道细菌的性传播性质， 用于女性生殖道疾病的临床管理。

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.