Engineering microbiota to optimize population-level health

工程微生物群以优化人群健康

基本信息

批准号：
10227108
负责人：
Karen J Guillemin
金额：
$ 28.43万
依托单位：
UNIVERSITY OF OREGON
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-06 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10227108
关键词：
Address Animals Anti-Inflammatory Agents Bacteria Cells Chronic Diabetes Mellitus Disease Distal Engineering Environment Gene Expression Genetic Models Gnotobiotic Health Health Status Herd Immunity Human Immune Immunocompromised Host Immunosuppression Individual Infection Infectious Agent Inflammation Inflammatory Inflammatory Bowel Diseases Inflammatory Response Intestines Knowledge Link Metabolic syndrome Microbe Modeling Play Population Positioning Attribute Probiotics Property Proteins Research Resistance Role Site Symptoms Testing Therapeutic Vaccination Zebrafish bacterial genetics design disease transmission dysbiosis experimental study genetic testing host microbiota inflammatory disease of the intestine innovation member microbial community microbiota novel pathogen prevent programs promoter prototype tool transmission process

项目摘要

PROJECT SUMMARY/ABSTRACT (PROJECT 3) Increasing numbers of human ailments, including inflammatory bowel disease (IBD), metabolic syndrome, and diabetes, have been linked to disturbances in resident microbial communities. In these diseases, no single infectious organism is implicated, but instead abnormal, also called dysbiotic microbial communities, often characterized by an overabundance of pro-inflammatory taxa and an underrepresentation of anti- inflammatory taxa, are implicated in causing disease symptoms. Mounting evidence suggests that pro- inflammatory microbiota can be self-perpetuating because the inflamed host environment selects for microbes that promote and thrive on conditions that perpetuate inflammation. We hypothesize that transmission of pro- inflammatory microbiota members increases the likelihood of developing disease, and that this transmission is enhanced by the absence of anti-inflammatory taxa that would normally curtail a chronically inflamed host environment. We hypothesize that transmissible anti-inflammatory strains would be useful not only for alleviating inflammation in individual hosts, but for spreading resistance to pro-inflammatory strains, thereby creating herd immunity to disease-causing strains similar to vaccination. We propose to engineer microbiota members that function as “smart probiotics” to sense and alleviate host inflammation in a modulated and local fashion. We will determine how to tune the therapeutic and transmission properties of these smart probiotics to optimize their capacity to treat inflammation in individual hosts and to disseminate sufficiently between hosts to generate protection against the spread of pro-inflammatory strains on a population scale. These experiments will establish the design principles for engineering transmissible health.

项目摘要/摘要（项目3）人类疾病的数量增加，包括炎症性肠病（IBD），代谢综合征，和糖尿病与居民微生物群落的干扰有关。感染性有牵连，但常常是异常的，也常常导致失调的生物微生物群落。其特征是促炎分类群和反抗性的特征炎症类群与引起疾病症状有关。炎症性微生物群可以自我延伸，因为发炎的宿主环境选择了微生物在炎症的情况下促进和壮成长。炎性菌群成员增加了发展疾病的可能性，而传播是由于缺乏抗炎类群而增强的，通常会减少长期发炎的宿主主机环境。减轻单个宿主的炎症，但由于对亲炎菌株的抗性扩散我们提出了类似于疫苗接种的引起疾病菌株的牛群免疫。作为“智能益生菌”功能的成员，以感知和减轻模块化和本地的宿主炎症时尚。优化其Capace以信任单个宿主的炎症，并在宿主可以在人口范围内保护促炎性菌株。实验将建立工程可传播健康的设计公主原理。