DESIGNING A HIGH-THROUGHPUT PLATFORM TO BIOPROSPECT THE HUMAN MICROBIOME AND MANIPULATE ITS INTERPLAY WITH HOST ENVIRONMENTS

设计一种高通量的人体微生物组生物检测平台 操控其与主机环境的相互作用 项目摘要 人类的微生物群由数百种生活在体内和身体上的微生物组成，现在人们已经认识到 在人类健康和绩效以及疾病预防和管理方面发挥关键作用。一个健康的人 微生物组(由于一些关键物种不能培养而尚未完全表征) 检查通常存在的有害微生物。然而，当这种平衡被扰乱时，致病 微生物可能会过度生长，这种情况被称为生物失调，并损害肠道和免疫功能。 迫切需要开发微生物群落的生长和操纵技术来 评估益生菌和合成社区的有益影响。发展这种能力将会 通过提供一组个性化的微生物，使临床医生能够扭转微生物失衡 恢复与感染、炎症、代谢、心血管和认知相关的肠道功能 病人中的疾病。为此，我的团队的目标是推进一种大胆而独特的基于微流体的技术，以 分离、培养、重建并长期操纵人类胃肠道(GI、肠道)微生物群 用来治疗疾病。本申请的具体目的是开发一种纳米培养系统来培养微生物分离物 来自肠道的，包括那些尚未培养的，并确定有益的相互作用或生物活性代谢物 对设计能够根除或抑制病原体生长的合成群落至关重要，例如 艰难梭菌。设计的社区的初步效果将通过治疗来确定 艰难梭菌感染(CDI)在已建立的小鼠模型中。我们的长期目标是开发一种微生物 人类起源的活体生物治疗学银行，包括适用于 个性化、精准化医疗。我们设想这项技术将是一项安全、易于交付和高效的 粪便微生物区系移植(FMT)的替代方案，用于治疗各种非生物条件，从而帮助恢复 健康的肠道微生物群。

DESIGNING A HIGH-THROUGHPUT PLATFORM TO BIOPROSPECT THE HUMAN MICROBIOME AND MANIPULATE ITS INTERPLAY WITH HOST ENVIRONMENTS Project Summary The human microbiome, comprising hundreds of microbial species living in and on the body, is now recognized to play critical roles in human health and performance as well as disease prevention and management. A healthy microbiome (which has not yet been fully characterized because some key species cannot be cultured) keeps in check harmful microbes that are normally present. However, when this balance is perturbed, pathogenic microbes may overgrow, a condition called dysbiosis, and compromise both gut and immune functions. Development of technologies for the growth and manipulation of microbial consortia are urgently needed to assess the beneficial effects attributed to probiotics and synthetic communities. Developing such ability would enable clinicians to reverse microbial imbalance by providing a personalized set of microorganisms capable of restoring gut functions associated with infectious, inflammatory, metabolic, cardiovascular, and cognitive diseases in patients. To this end, my group aims to advance a bold and unique microfluidic-based technology to isolate, culture, reconstruct, and, in the long-term, manipulate the human gastrointestinal (GI, gut) microbiome to treat diseases. This application specifically aims to develop a nanoculture system to grow microbial isolates from the gut, including those as yet unculturable, and identify beneficial interactions or bioactive metabolites essential to design synthetic communities capable of eradicating or inhibiting the growth of pathogens such as Clostridium difficile. The preliminary effectiveness of the ‘designed’ communities will be determined by treating Clostridium difficile Infection (CDI) in an established mouse model. Our long-term goal is to develop a microbial bank of live biotherapeutics of human origin comprising defined microbial communities applicable for personalized and precision medicine. We envision this technology to be a safe, easy-to-deliver, and efficient alternative to fecal microbiota transplant (FMT) to treat diverse dysbiotic conditions, and thus help restore a healthy gut microbiome.