Microbiota-immune interactions that promote intestinal homeostasis

促进肠道稳态的微生物群-免疫相互作用

• 批准号: 10211299
• 负责人: June Louise Round
• 金额: $ 60.61万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10211299
• 关键词: Adipose tissue; Age; Animals; Bacteria; Binding; CD36 Antigens; CD36 gene; Ceramides; Chronic; Colitis; Collection; Communities; Complex; Crohn' s disease; Data; Defect; Desulfovibrio; Development; Diabetes Mellitus; Disease; Disease Progression; Disease model; Gnotobiotic; Human; Immune; Immune system; Immunity; Immunoglobulin A; Incidence; Individual; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Insulin Resistance; Intestinal permeability; Intestines; Investigation; Lead; Link; Lipids; Maintenance; Metabolic; Metabolic Diseases; Metabolic syndrome; Metabolism; Metagenomics; Microbe; Obesity; Oral; Organism; Pathway interactions; Patients; Population; Prevention; Production; Publishing; Relapse; Role; Sampling; Series; Systems Development; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Uses; Ulcerative Colitis; Weight Gain; absorption; base; commensal bacteria; experimental study; gut health; gut homeostasis; gut microbes; inflammatory disease of the intestine; intestinal homeostasis; member; microbial; microbial composition; microbiota; microbiota transplantation; microorganism interaction; mouse model; novel; novel marker; prevent; response; sulfate reducing bacteria; therapeutic development

ABSTRACT Individuals with inflammatory bowel disease (IBD) are more likely to develop metabolic abnormalities, such as diabetes, however little is known about the basis of this connection. Multiple studies have now shown that changes to the composition of the microbiota are a factor in multiple diseases, including IBD and diabetes. Moreover, the studies that have examined the composition of the microbiota within individuals with IBD or diabetes, have identified similar changes to these resident communities. We have recently identified a mouse model that develops worsened colitis and spontaneous obesity and insulin resistance. Both of these diseases are reliant on the microbiota and can be rescued by a microbiota transplant, or an oral gavage of a purified population of Clostridia. Thus, we hypothesize that the growing incidence of IBD and diabetes may be attributable to similar defects in the microbiota and might explain the why some individuals are more prone to develop both diseases. Based on this, we propose a series of experiments to identify a defined consortia of Clostridia that will function to prevent disease and explore the common mechanisms, including effects of the immune system, between IBD and metabolism that might lead to the development of these diseases. Thus, our findings will be among the first to identify a consortia of bacteria that could be used for therapeutic intervention/prevention of IBD and/or diabetes and allow for an in-depth mechanistic understanding of how these protective bacteria maintain intestinal homeostasis.

摘要 炎症性肠病（IBD）患者更容易发生代谢异常，如 糖尿病，但对这种联系的基础知之甚少。多项研究表明， 微生物群组成的变化是多种疾病的因素，包括IBD和糖尿病。 此外，研究了IBD或IBD患者体内微生物群的组成， 糖尿病，已经确定了这些居民社区的类似变化。我们最近发现了一种老鼠 发展恶化的结肠炎、自发性肥胖和胰岛素抵抗的模型。这两种疾病 依赖于微生物群，可以通过微生物群移植或口服经纯化的 Clostridia的人口。因此，我们假设IBD和糖尿病发病率的增加可能是 可归因于微生物群中的类似缺陷，并可能解释为什么有些人更容易患上 这两种疾病的发展。在此基础上，我们提出了一系列的实验，以确定一个定义的财团， 梭菌，将发挥作用，以预防疾病，并探讨共同的机制，包括影响的 免疫系统，IBD和代谢之间，可能导致这些疾病的发展。所以我们 这些发现将是第一个确定一个可用于治疗的细菌财团。 干预/预防IBD和/或糖尿病，并允许深入了解如何 这些保护性细菌维持肠道内环境稳定。