Model-guided design of next-generation bacterial therapeutics to treat cardiovascular disease

项目摘要/摘要 越来越明显的是，人类肠道微生物群产生的成分和代谢物 影响心血管疾病的进展。当我们继续发现重要的联系时 在肠道微生物群与人类生理和疾病之间，我们缺乏工具和方法来 精确操纵肠道微生物区系，造福人类健康。我们建议开发计算模型和 预测社区动态和功能的优化框架，并设计干预措施以转移胆量 微生物群达到所需状态。我们将设计新的细菌疗法，在 哺乳动物的胃肠道将微生物群引向健康状态。这些下一代 细菌疗法将感知重要的肠道微生物组代谢物，处理信息，并传递物种- 特定的抗微生物蛋白质，以重塑这一生态系统的动态和功能。的表现 这些细菌疗法将使用合成的人类肠道微生物群落在体外进行表征 在心血管疾病的诺生菌小鼠模型中。模型引导的微生物组工程具有 改变人类医学的潜力，随着科学家不断发现，它正变得越来越重要 微生物群与人类健康和疾病之间的联系。

PROJECT SUMMARY/ABSTRACT It is becoming increasingly evident that the composition and metabolites produced by the human gut microbiome influence the progression of cardiovascular diseases. While we are continuing to discover important associations between the gut microbiome and human physiology and diseases, we lack the tools and methodology to precisely manipulate gut microbiota to benefit human health. We propose to develop computational models and optimization frameworks to predict community dynamics and functions and design interventions to shift the gut microbiome to desired states. We will design novel bacterial therapeutics that operate autonomously in the mammalian gastrointestinal tract to steer the microbiome towards healthy states. These next-generation bacterial therapeutics will sense important gut microbiome metabolites, process information, and deliver species- specific antimicrobial proteins to reshape the dynamics and functions of this ecosystem. The performance of these bacterial therapeutics will be characterized in vitro using synthetic human gut microbiome communities and in gnotobiotic mouse models of cardiovascular disease. Model-guided microbiome engineering has the potential to transform human medicine and is becoming increasingly important as scientists continue to discover connections between the microbiome and human health and disease.