Altered Microbiome of Chronic Pelvic Pain

 描述(由申请人提供)：胃肠道中存在着丰富多样的细菌物种，构成了胃肠道“微生物群”的主体。胃肠道微生物群在全身的健康和疾病过程中发挥着关键作用，但目前尚不清楚该微生物群是否或如何介导了泌尿系慢性盆腔疼痛综合征(UCPPS)的发病机制。事实上，UCPPS在女性和男性中都会导致显著的发病率，但缺乏病因、诊断标记和治疗方法。在这里，我们提供的初步数据表明，女性的UCPPS与改变的胃肠道微生物区系有关，特定物种是新的UCPPS生物标记物的候选对象。此外，在临床相关的小鼠UCPPS模型中，可以通过操纵GI微生物组来调节症状样行为。我们假设，改变的胃肠道微生物群导致作用于中枢神经系统靶点的循环细菌产物，并对UCPPS做出贡献。该项目将结合临床、翻译和机械学研究来确定胃肠道微生物群在UCPPS中的作用，并与无疼痛的排尿功能障碍形成对比。这些发现将导致开发新的诊断方法和有效的益生菌治疗慢性盆腔疼痛。

 DESCRIPTION (provided by applicant): Abundant and diverse bacterial species inhabit the GI tract, constituting the bulk of the GI "microbiome." The GI microbiome plays key roles in health and disease processes throughout the body, yet it is unclear whether or how the microbiome mediates the pathogenesis of urologic chronic pelvic pain syndromes (UCPPS). Indeed, UCPPS cause significant morbidity in women and men, but etiologies, diagnostic markers, and therapies are lacking. Here, we present preliminary data demonstrating that UCPPS in women is associated with altered GI microbiota, and specific species are candidates for novel UCPPS biomarkers. Moreover, in clinically relevant murine UCPPS models, symptom-like behaviors can be modulated by manipulating the GI microbiome. We hypothesize that an altered GI microbiome results in circulating bacterial products that act on CNS targets and contribute to UCPPS. This project will use a combination of clinical, translational, and mechanistic studies to define the role of the GI microbiome in UCPPS, and in contrast to voiding dysfunction in the absence of pain. These findings will lead to the development of novel diagnostics and effective probiotic therapies for chronic pelvic pain.