Altered Microbiome of Chronic Pelvic Pain

慢性盆腔疼痛的微生物组改变

• 批准号: 9038126
• 负责人: David J Klumpp
• 金额: $ 55.16万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-18 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9038126
• 关键词: Adrenal Glands; Anxiety; Bacteria; Behavior; Biological Markers; Brain; Brain region; Cell Nucleus; Chronic Prostatitis; Clinical; Clinical Trials; Computer Simulation; Corticotropin-Releasing Hormone; Cystitis; Data; Development; Diagnostic; Disease; Disease Marker; Escherichia coli; Etiology; Evaluation; Feces; Female; Functional disorder; Gastrointestinal tract structure; Genetic study; Health; Human Microbiome; Hypothalamic structure; In Vitro; Infection; Interstitial Cystitis; Lead; Link; Machine Learning; Mediating; Mediator of activation protein; Mental Depression; Modeling; Molecular; Morbidity - disease rate; Mus; Neurogenic Inflammation; Oral; Organ; Pain; Pathogenesis; Patients; Pelvic Pain; Pelvis; Phenotype; Pituitary Gland; Play; Probiotics; Process; Protocols documentation; Recombinant DNA; Role; Sampling; Serum; Shapes; Staging; Symptoms; Tactile; Taxon; Testing; Urinary tract infection; Urine; Vagina; Visceral; Wild Type Mouse; Woman; allodynia; chronic pelvic pain; clinically relevant; comparative; computerized tools; diagnostic biomarker; effective therapy; hypothalamic-pituitary-adrenal axis; men; metagenome; microbial; microbiome; microbiota; mouse model; novel; novel diagnostics; paraventricular nucleus; patient subsets; probiotic therapy; public health relevance; small molecule; urinary; urologic

 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.

 描述（由适用提供）：丰富的潜水细菌居住在胃肠道中，构成了GI的大部分“微生物组”。 GI微生物组在整个身体的健康和疾病过程中起关键作用，但尚不清楚微生物组是否或如何介导泌尿科慢性骨盆疼痛综合征（UCPPS）的发病机理。实际上，UCPP在男女中引起了显着的发病率，但是缺乏病因，诊断标记和疗法。在这里，我们提供了初步数据，表明女性的UCPP与胃肠道菌群的改变有关，而特定物种是新型UCPPS生物标志物的候选者。此外，在临床相关的鼠UCPP模型中，可以通过操纵胃肠道微生物组来调节症状样行为。我们假设改变的GI微生物组会导致对CNS靶标作用并促进UCPP的细菌产物。该项目将结合临床，翻译和机理研究来定义胃肠道微生物组在UCPP中的作用，并且与在没有疼痛的情况下无效的功能障碍相反。这些发现将导致新的诊断和有效益生菌疗法的慢性疼痛发展。