Microbiomes of Interstitial Cystitis

描述(申请人提供)：间质性膀胱炎/痛性膀胱综合征(IC)是一种毁灭性的疾病，其特征是严重的盆腔疼痛和排尿功能障碍。尽管多年来的研究，IC的病因或广泛有效的治疗方法尚不存在，这表明需要考虑新的想法和方法。根据几条证据，“微生物组”是一个新兴的研究领域，有可能在我们对I的理解中发挥重要作用。首先，许多IC患者表现出G1或生殖道共病。其次，证实了膀胱、膀胱、生殖道之间存在串扰。第三，我们发现细菌可以调节一系列盆腔疼痛反应，从疼痛抑制到引起慢性疼痛。第四，微生物菌群密集分布在某些身体部位，数量确实超过了人类细胞，新的发现表明，改变的微生物群可能会导致复杂的疾病。因此，我们将发展一个跨学科的团队来解决这个新的问题：胃肠道和/或生殖道微生物群的改变是否与IC有关？我们的团队将结合IC的临床专业知识、确定Gl和生殖道微生物群的方法学和生物学专业知识，以及骨盆疼痛的微生物基础专业知识。我们的团队将利用这些关键领域的协同效应来开发特定的假设和战略，以定义微生物群和IC之间的关联。此外，将开发临床相关的小鼠模型，以建立微生物群改变和骨盆疼痛调制之间的因果联系。明确IC微生物群对于了解IC的病因、机制和治疗具有潜在的重要意义。IC患者通常有使用抗生素治疗尿路感染的病史，但抗生素可以改变微生物 多样性，从而导致疾病。IC微生物群的改变可能通过器官串扰或扩大的尿路病原体储存库导致盆腔疼痛的功能失调。最后，微生物群的操作在其他临床专科中被证明是有效的，这表明有可能对IC进行方便的益生菌治疗。 与公共卫生相关：间质性膀胱炎/痛性膀胱综合征(IC)是一种慢性膀胱疾病，无不明原因或有效治疗，使人衰弱。这项研究将建立一个跨学科的团队来探索这个新的问题，即胃肠道和生殖道中大型细菌群落的变化是否在IC中起到因果作用。

DESCRIPTION (provided by applicant): Interstitial cystitis/painful bladder syndrome (IC) is a devastating condition characterized by severe pelvic pain and voiding dysfunction. Despite years of investigation, no etiology or widely effective therapies exist for IC, indicating the needto consider new ideas and approaches. Based on several lines of evidence, the "microbiome" is an emerging field of study that has the potential to play a significant role in our understanding of I. First, many IC patients exhibit Gl or reproductive tract co-morbidities. Second, it is established that crosstalk exists among the bladder, Gl tract, and reproductive tract. Third, we find that bacteria can mediate a range of pelvic pain responses, from pain suppression to causing chronic pain. Fourth, microbial flora densely populate certain body sites, indeed outnumbering human cells, and new findings demonstrate that altered microbiomes can drive complex diseases. We therefore will develop an interdisciplinary team to address this novel question: is an altered gastrointestinal and/or reproductive tract microbiome associated with IC? Our team will bring together clinical expertise in IC, methodologic and biologic expertise in defining microbiomes of the Gl and reproductive tracts, and expertise in the microbial basis of pelvic pain. Our team will exploit the synergies from these key fields to develop specific hypotheses and strategies for defining associations between microbiomes and IC. Moreover, clinically relevant murine models will be developed to establish a causal link between altered microbiomes and modulation of pelvic pain. Defining IC microbiomes has potentially major significance for understanding IC etiology, mechanisms, and treatments. IC patients often have a history of antibiotic treatments for urinary tract infection, yet antibiotics can shift microbial diversity and thereby cause disease. Altered IC microbiomes could result in dysfunctional modulation of pelvic pain via organ crosstalk or expanded reservoirs of uropathogens. Finally, manipulation of microbiomes is proving efficacious in other clinical specialties, suggesting the possibility of possibility of convenient probiotic therapies for IC. PUBLIC HEALTH RELEVANCE: Interstitial cystitis/painful bladder syndrome (IC) is a debilitating chronic bladder condition without known cause or effective treatments. This study will develop an interdisciplinary team to explore the novel question of whether alterations in the large bacterial communities that populate the gastrointestinal and reproductive tracts play a causal role in IC.