Engineering microbiota to optimize population-level health

项目总结/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，都与当地微生物群落的紊乱有关。在这些疾病中， 感染性微生物是牵连的，而是异常的，也称为生态失调的微生物群落，通常 其特征是促炎分类群过多，而抗炎分类群代表性不足。 炎性分类群与引起疾病症状有关。越来越多的证据表明，亲- 炎症微生物群可以自我延续，因为发炎的宿主环境选择微生物， 在炎症持续存在的条件下促进和生长。我们假设亲- 炎症微生物群成员增加了发展疾病的可能性，这种传播是 由于缺乏通常会减少慢性炎症宿主的抗炎分类群而增强 环境我们假设，可传播的抗炎菌株不仅对 减轻个体宿主的炎症，但传播对促炎菌株的抗性，从而 产生类似于疫苗接种的对致病菌株的群体免疫。我们建议设计微生物群 作为“智能益生菌”的成员，以调节和局部的方式感知和减轻宿主炎症， 时尚.我们将确定如何调整这些智能益生菌的治疗和传输特性 以优化其治疗个体宿主炎症的能力，并在宿主之间充分传播， 宿主以产生针对促炎菌株在群体规模上的传播的保护。这些 实验将建立工程可传播健康的设计原则。

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.