Engineering microbiota to optimize population-level health

工程微生物群以优化人群健康

• 批准号: 10468041
• 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
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-06 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10468041
• 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; gut inflammation; host microbiota; innovation; member; microbial community; microbiota; novel; pathogen; prevent; programs; promoter; prototype; tool; transmission process

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） 越来越多的人类疾病，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灾难有关。在这些疾病中，没有一个 隐含感染性有机体，但是异常，也称为不植物微生物群落，通常 其特征是促炎的分类单元过多，反抗药性不足 炎症类群与引起疾病症状有关。越来越多的证据表明 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 这会促进和壮成长，以使注射永存。我们假设促进的传播 炎症性微生物群会员增加了疾病的可能性，并且这种传播是 由于缺乏通常会减少长期发炎的宿主的抗炎类群而增强 环境。我们假设可传播的抗炎菌株不仅对 减轻各个宿主的感染，但由于对促炎性菌株的抗性扩散 产生类似于疫苗的菌株的牛群免疫学。我们建议设计微生物群 作为“智能益生菌”功能的成员，可以在调制和本地中感知和减轻宿主注入 时尚。我们将确定如何调整这些智能益生菌的治疗和传播特性 优化其治疗单个宿主感染的能力，并在 宿主以保护促炎性菌株在人群量表上的传播。这些 实验将建立工程可传播健康的设计原则。