Altered Microbiome of Chronic Pelvic Pain

 描述（由申请方提供）：丰富多样的细菌物种栖息在胃肠道中，构成了胃肠道微生物组的主体。“GI微生物组在整个身体的健康和疾病过程中起着关键作用，但目前还不清楚微生物组是否或如何介导泌尿系慢性盆腔疼痛综合征（UCPPS）的发病机制。事实上，UCPPS在女性和男性中引起显著的发病率，但缺乏病因学，诊断标志物和治疗方法。在这里，我们提出的初步数据表明，女性的UCPPS与GI微生物群的改变有关，特定的物种是新型UCPPS生物标志物的候选者。此外，在临床相关的鼠UCPPS模型中，可以通过操纵GI微生物组来调节胃肠道样行为。我们假设GI微生物组的改变导致循环细菌产物作用于CNS靶点并促成UCPPS。该项目将使用临床，转化和机制研究的组合来定义GI微生物组在UCPPS中的作用，并与没有疼痛的排尿功能障碍形成对比。这些发现将导致慢性盆腔疼痛的新型诊断和有效的益生菌疗法的发展。

 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.