Bacterial, Viral, and Host Interactions in the Pathogenesis of Inflammatory Bowel Disease

炎症性肠病发病机制中的细菌、病毒和宿主相互作用

基本信息

批准号：
10657414
负责人：
Kira Newman
金额：
$ 8.37万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10657414
关键词：
Address Adult Affect Animal Model Automobile Driving Bacteria Bacterial Genome Bacteriophages Basic Science Biological Models Chronic Clinical Colitis Communication Communities Complex Cytolysis Data Development Disease Enterobacteriaceae Experimental Designs Feces Fellowship Filtration Flare Fostering Foundations Funding Gastroenterologist Gastroenterology Germ-Free Goals Human Human Microbiome Immunologics Immunology Individual Inflammation Inflammatory Inflammatory Bowel Diseases Interferon Type II K-Series Research Career Programs Knowledge Literature Maintenance Medical Mentorship Metabolic Metabolic Pathway Metabolism Metagenomics Methodology Michigan Modeling Modification Molecular Mus Observational Study Oral Participant Pathogenesis Pathology Pathway interactions Patients Pharmaceutical Preparations Physiological Predisposition Prevalence Prevention Research Research Personnel Role Severities Shapes Stress T-Cell Activation Therapeutic Time Training Translational Research United States Universities Viral Virus Work Writing bacterial community bacterial fitness bacteriome burden of illness career career development dysbiosis fecal microbiome fecal transplantation gut bacteria gut inflammation gut microbiome gut microbiota host microbiome humanized mouse improved metabolome microbial microbiome microbiome alteration microbiome components microbiota mouse model new therapeutic target novel novel therapeutic intervention novel therapeutics pathobiont predict clinical outcome prediction algorithm response skills trend virome

项目摘要

PROJECT SUMMARY/ABSTRACT Inflammatory bowel disease (IBD) affects an estimated 1.3% of adults in the United States and is increasing in prevalence globally. Host-microbiome interactions are an important contributor to IBD pathogenesis and disease flares, but the role of non-bacterial components of the microbiome, such as eukaryotic viruses and viruses that infect bacteria (bacteriophages), are less understood. Therefore, we propose a study of the effect of the viral component of the microbiome (i.e. virome) on IBD pathogenesis. Preliminary studies suggest that stool from humans with IBD is pro-inflammatory, even when combined with stool from healthy individuals. However the factors driving this effect are not fully known. We hypothesize that the virome in IBD exerts a pro- inflammatory effect through modulation of the bacterial microbiota. Improved understanding of the role of viruses in IBD will inform the development of microbial therapeutics and prediction of clinical outcomes. This study’s goal is to characterize the effects of fecal virome transfer on colitis using a humanized mouse model. To address this goal, we propose: 1. To quantify the changes in host pathology, molecular pathways, and bacterial communities following fecal viral transfer and 2. To evaluate whether changes in IBD disease activity in patients is accompanied by changes in fecal viruses and their inflammatory effects. The fellowship applicant aspires to become an independent investigator and academic gastroenterologist, with most of her time spent conducting translational and basic science research. Her long-term goal is to understand the role of viruses in the maintenance of microbiome stability and response to stress in IBD to develop novel targets for treatment and prevention. Under this fellowship, she will acquire a rigorous methodological foundation in immunology and microbial ‘omics through coursework and interdisciplinary mentorship. This training will be essential to address the proposed research question, develop the skills necessary as an independent investigator, and achieve her long-term career goals. Specific goals for this fellowship include: 1. Developing expertise in the analysis of viral metagenomic data, 2. Fostering high proficiency in mechanistic microbiota-based experimental design, 3. Building excellence in the use of animal models for IBD, 4. Maintaining an active understanding of trends and developments in human immunology, microbial ‘omics, and translational research in inflammatory bowel disease, 5. Continued communication of findings through scientific writing and oral presentations, and 6. Actively pursuing career development opportunities to support transitioning to independence. At the start of the funding period, the applicant will have already completed one year of clinical gastroenterology training and one year of basic science training on a T32 at the University of Michigan.

项目概要/摘要据估计，美国 1.3% 的成年人患有炎症性肠病 (IBD)，并且患病人数正在增加宿主与微生物组的相互作用是 IBD 发病机制的一个重要因素。疾病爆发，但微生物组非细菌成分的作用，例如真核病毒和感染细菌（噬菌体）的病毒知之甚少，因此，我们建议对其影响进行研究。微生物组的病毒成分（即病毒组）对 IBD 发病机制的影响。患有 IBD 的人的粪便具有促炎性，即使与健康人的粪便相结合也是如此。然而，驱动这种效应的因素尚不完全清楚，我们努力了解 IBD 中的病毒组发挥着亲-作用。通过调节细菌微生物群的炎症作用提高了对其作用的了解。 IBD 中的病毒将为微生物疗法的开发和临床结果的预测提供信息。研究的目标是利用人源化小鼠模型来表征粪便病毒组转移对结肠炎的影响。为了实现这一目标，我们建议： 1. 量化宿主病理学、分子途径和 2. 评估 IBD 疾病活动性是否发生变化患者的肠道菌群变化伴随着粪便病毒及其炎症效应的变化。渴望成为一名独立研究者和学术胃肠病学家，她的大部分时间都花在她的长期目标是了解病毒在转化和基础科学研究中的作用。维持 IBD 中微生物群的稳定性和对应激的反应，以开发新的治疗靶点在该奖学金的资助下，她将获得严格的免疫学方法学基础。通过课程作业和跨学科指导进行微生物组学培训至关重要。解决拟议的研究问题，培养作为独立调查员的必要技能，以及实现她的长期职业目标。该奖学金的具体目标包括： 1. 发展该领域的专业知识。病毒宏基因组数据分析，2. 培养基于机械微生物群的实验的高熟练度设计，3. 建立卓越的 IBD 动物模型使用，4. 保持积极的理解人类免疫学、微生物组学和炎症转化研究的趋势和发展肠道疾病，5. 通过科学写作和口头陈述持续交流研究结果，以及 6. 在开始时积极寻求职业发展机会以支持向独立过渡。资助期内，申请人已完成一年的临床胃肠病学培训，并且在密歇根大学 T32 上接受一年的基础科学培训。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

A Systematic Review of Inflammatory Bowel Disease Epidemiology and Health Outcomes in Sexual and Gender Minority Individuals.

对性和性别少数人群炎症性肠病流行病学和健康结果的系统评价。

DOI：
发表时间：
2023-05
期刊：
影响因子：
0
作者：
Newman, Kira L;Chedid, Victor G;Boden, Elisa K
通讯作者：
Boden, Elisa K

Response to Mansoor et al: 'epidemiology of inflammatory bowel disease in men with high-risk homosexual activity'.

对 Mansoor 等人的回应：“具有高风险同性恋活动的男性炎症性肠病的流行病学”。

DOI：
发表时间：
2023-10
期刊：
影响因子：
24.5
作者：
Newman, Kira L;Jencks, Kara;Chedid, Victor;Paul, Sonali;Higgins, Peter D R;Kane, Sunanda V;Long, Millie
通讯作者：
Long, Millie