Functional Considerations of the Urinary Microbiome in Overactive Bladder

膀胱过度活动症中尿液微生物组的功能考虑

• 批准号: 10132307
• 负责人: Lisa Anne Karstens
• 金额: $ 13.59万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-06-01 至 2023-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10132307
• 关键词: Adult; Affect; American; Analytical Chemistry; Bacteria; Bioinformatics; Biological Markers; Biomedical Research; Bladder; Bladder Diseases; Clinical; Clinical Management; Clinical Research; Complex; Data; Development; Development Plans; Diagnostic; Disease; Economics; Emotional; Environment; Etiology; Frequencies; Functional disorder; Goals; Health; Health Sciences; Immune response; Immune system; Immunoglobulin A; Immunology; Incontinence; Infection; Inflammatory; Institution; Intestinal Motility; Irritable Bowel Syndrome; Knowledge; Light; Lower urinary tract; Measures; Mentors; Mentorship; Metabolic; Methods; Microbe; Microbiology; Molecular; NMR Spectroscopy; Nocturia; Oregon; Organ; Outcome; Overactive Bladder; Pathogenicity; Patients; Play; Quality of life; Research; Research Infrastructure; Research Personnel; Research Support; Research Training; Role; Site; Sterility; Symptoms; Syndrome; Techniques; Technology; Testing; Therapeutic; Training; Training Programs; Training and Infrastructure; Translational Research; Universities; Urge Incontinence; Urinary Incontinence; Urinary Microbiome; Urinary tract; Urine; Urologic Diseases; Vagina; Woman; Women' s Health; Work; acute infection; career; career development; cell motility; collaborative environment; commensal microbes; common symptom; economic cost; fungus; gut microbiota; host-microbe interactions; immunogenic; improved; infancy; insight; knowledge base; metabolomics; microbial; microbial community; microbiota; micturition urgency; neuromuscular function; novel; patient population; small molecule; social; targeted treatment; therapeutically effective; treatment strategy; urinary

Project Summary Overactive bladder (OAB) is a symptom complex that is highly prevalent and negatively impacts quality of life. Multiple mechanisms likely contribute to OAB symptoms, though current therapies only target a few potential mechanisms. Recent evidence suggests that the urinary tract, which traditionally has been thought to be sterile in the absence of a clinically identifiable infection, actually harbors a variety of microbes, known collectively as the urinary microbiota, even when clinical cultures are negative. These microbial communities appear to be altered women with urge urinary incontinence (wet OAB), however it is unknown if the urinary microbiota are also altered in the broader patient population with OAB without incontinence (dry OAB) or how the urinary microbiota contribute to OAB symptoms. This proposal aims to determine if the urinary microbiota are also altered in women with dry OAB (Aim 1). Additionally, the proposed study also aims to lay the ground work for understanding the functional contribution of the urinary microbiota to OAB. In other body sites, commensal microbes contribute to host health and disease through interactions with the immune system and their metabolic activity. The proposed studies will identify interactions with the host immune system by identifying immunoglobulin-A associated microbes (Aim 2) and identify metabolic products of the urinary microbiota through metabolomics studies (Aim 3). Together, information gained through completion of these aims will lead to key insights that will guide biomarker and mechanistic studies aimed at improving the clinical management of patients with OAB. Candidate: Dr. Karstens has a unique background including training in bioinformatics and analytical chemistry. Her long-term goals are to apply this knowledge to understand the mechanisms underlying complex urinary tract disorders to streamline therapeutic options for women suffering from these conditions. Career development plan: The career development plan includes hands-on and didactic training to gain expertise in women’s health and clinical research, as well as expand her knowledge in the molecular techniques required to understand the function of the urinary microbiota. Environment: Her interdisciplinary mentorship team brings together expertise in bioinformatics (Dr. McWeeney), urogynecology (Dr. Gregory), microbiology (Dr. Wolfe), immunology (Dr. Rosenbaum), and host-microbe interactions (Dr.Braun). Training will be completed at Oregon Health & Science University, a leading biomedical research and training institution in the state of Oregon. OHSU has an excellent translational research and training infrastructure to facilitate the successful transition to an independent career in translational bioinformatics research focused on understanding bladder disorders. !

项目概要 膀胱过度活动症 (OAB) 是一种非常普遍的症状，会对生活质量产生负面影响。 尽管目前的治疗仅针对少数潜在的症状，但多种机制可能会导致 OAB 症状 机制。最近的证据表明，传统上被认为是无菌的泌尿道 在没有临床可识别的感染的情况下，实际上含有多种微生物，统称为 尿液微生物群，即使临床培养结果呈阴性。这些微生物群落似乎 患有急迫性尿失禁（湿性 OAB）的女性发生了改变，但尚不清楚尿微生物群是否会改变。 在更广泛的患有 OAB 但不伴有失禁（干性 OAB）的患者群体中，尿频或尿频也发生了改变。 微生物群会导致 OAB 症状。该提案旨在确定尿液微生物群是否也与 患有干性 OAB 的女性发生了改变（目标 1）。此外，拟议的研究还旨在为以下方面奠定基础： 了解尿液微生物群对 OAB 的功能贡献。在其他身体部位，共生 微生物通过与免疫系统及其免疫系统的相互作用促进宿主健康和疾病 代谢活动。拟议的研究将通过识别与宿主免疫系统的相互作用来确定 免疫球蛋白-A 相关微生物（目标 2）并鉴定尿液微生物群的代谢产物 通过代谢组学研究（目标 3）。总之，通过完成这些目标获得的信息将引导 指导旨在改善临床管理的生物标志物和机制研究的关键见解 OAB 患者。候选人：Karstens 博士拥有独特的背景，包括生物信息学和 分析化学。她的长期目标是应用这些知识来理解机制 潜在的复杂泌尿道疾病，以简化患有这些疾病的女性的治疗选择 状况。职业发展计划：职业发展计划包括实践和教学培训 获得女性健康和临床研究方面的专业知识，并扩展她在分子生物学方面的知识 了解尿液微生物群功能所需的技术。环境：她的跨学科 导师团队汇集了生物信息学（McWeeney 博士）、泌尿妇科（Gregory 博士）、 微生物学（沃尔夫博士）、免疫学（罗森鲍姆博士）和宿主-微生物相互作用（布劳恩博士）。培训将 在俄勒冈健康与科学大学完成，该大学是美国领先的生物医学研究和培训机构 俄勒冈州。 OHSU 拥有优秀的转化研究和培训基础设施，以促进 成功过渡到转化生物信息学研究的独立职业，重点关注 了解膀胱疾病。 ！

项目成果

Cohort-based learning for microbiome research community standards.

微生物组研究社区标准的基于队列的学习。

• DOI: 10.1038/s41564-023-01361-7
• 发表时间: 2023
• 期刊: Nature microbiology
• 影响因子: 28.3
• 作者: Kelliher,JuliaM;Rudolph,Marisa;Vangay,Pajau;Abbas,Arwa;Borton,MikaylaA;Davenport,EmilyR;Davenport,KarenW;Erazo,NataliaG;Herman,Chloe;Karstens,Lisa;Kocurek,Brandon;Lutz,HollyL;Myers,KevinS;Ockert,Ingrid;Rodriguez,Francis
• 通讯作者: Rodriguez,Francis

microshades: An R Package for Improving Color Accessibility and Organization of Microbiome Data.

• DOI: 10.1128/mra.00795-22
• 发表时间: 2022-11-17
• 期刊: Microbiology resource announcements
• 影响因子: 0.8

Forming Consensus To Advance Urobiome Research.

• DOI: 10.1128/msystems.01371-20
• 发表时间: 2021-08-31
• 期刊: mSystems
• 影响因子: 6.4
• 作者: Brubaker L;Gourdine JF;Siddiqui NY;Holland A;Halverson T;Limeria R;Pride D;Ackerman L;Forster CS;Jacobs KM;Thomas-White KJ;Putonti C;Dong Q;Weinstein M;Lukacz ES;Karstens L;Wolfe AJ
• 通讯作者: Wolfe AJ

Updating Urinary Microbiome Analyses to Enhance Biologic Interpretation.

• DOI: 10.3389/fcimb.2022.789439
• 发表时间: 2022
• 期刊: Frontiers in cellular and infection microbiology
• 影响因子: 5.7