Microbiomes of Interstitial Cystitis

间质性膀胱炎的微生物组

• 批准号: 8257609
• 负责人: David J Klumpp
• 金额: $ 35万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-15 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8257609
• 关键词: 18 year old; 21 year old; Address; Adult; Antibiotic Therapy; Antibiotics; Bacteria; Bladder; Cells; Child; Chronic; Clinical; Communities; Comorbidity; Complex; Disease; Etiology; Exhibits; Functional disorder; Human; Interstitial Cystitis; Investigation; Link; Mediating; Modeling; Mus; Organ; Pain; Patients; Pelvic Pain; Play; Probiotics; Recording of previous events; Role; Site; Urinary tract infection; Uropathogen; base; chronic pain; clinically relevant; effective therapy; field study; gastrointestinal; medical specialties; microbial; microbiome; novel; painful bladder syndrome; reproductive; response

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.

描述（由申请人提供）：间质性膀胱炎/膀胱疼痛综合征（IC）是一种以严重盆腔疼痛和排尿功能障碍为特征的破坏性疾病。尽管多年的研究，没有病因或广泛有效的治疗方法存在，表明需要考虑新的想法和方法。基于几种证据，“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Gl或生殖道合并症。第二，确定膀胱、泌尿道和生殖道之间存在串扰。第三，我们发现细菌可以介导一系列骨盆疼痛反应，从疼痛抑制到引起慢性疼痛。第四，微生物菌群密集地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，改变的微生物群可以驱动复杂的疾病。因此，我们将建立一个跨学科的团队来解决这个新问题：胃肠道和/或生殖道微生物群的改变是否与IC有关？我们的团队将汇集IC的临床专业知识，确定Gl和生殖道微生物组的方法学和生物学专业知识，以及盆腔疼痛微生物基础的专业知识。我们的团队将利用这些关键领域的协同作用来制定特定的假设和策略，以确定微生物组与IC之间的关联。此外，将开发临床相关的小鼠模型，以建立改变的微生物组与骨盆疼痛调节之间的因果关系。定义IC微生物组对于理解IC的病因、机制和治疗具有潜在的重要意义。IC患者通常有抗生素治疗尿路感染的历史，但抗生素可以转移微生物