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

构建一个高通量平台来生物勘探人体微生物， 操纵其与主机环境的交互 项目摘要 人体微生物组由生活在体内和体表的数百种微生物组成， 在人类健康和表现以及疾病预防和管理方面发挥关键作用。一个健康 微生物组（由于一些关键物种无法培养，因此尚未完全表征） 来检查正常存在的有害微生物。然而，当这种平衡被扰乱时， 微生物可能会过度生长，这种情况称为生态失调，并损害肠道和免疫功能。 迫切需要开发用于微生物聚生体的生长和操作的技术， 评估益生菌和合成菌群的有益效果。培养这种能力， 使临床医生能够通过提供一组个性化的微生物来扭转微生物失衡 恢复肠道功能与感染，炎症，代谢，心血管和认知相关 患者的疾病。为此，我的团队旨在推进一种大胆而独特的基于微流体的技术， 分离，培养，重建，并在长期内，操纵人类胃肠道（GI，肠道）微生物组 来治疗疾病本申请的具体目的是开发一种纳米培养系统，以培养微生物分离株 从肠道，包括那些尚未培养，并确定有益的相互作用或生物活性代谢物 设计能够根除或抑制病原体生长的合成群落至关重要， 艰难梭菌。“设计”社区的初步有效性将通过以下方式确定： 已建立的小鼠模型中的艰难梭菌感染（CDI）。我们的长期目标是开发一种微生物 包含确定的微生物群落的人源活生物治疗剂库，其适用于 个性化和精准医疗我们设想这项技术是一种安全、易于交付、高效的 粪便微生物群移植（FMT）的替代方案，以治疗各种生态失调状况，从而帮助恢复 健康肠道微生物组。

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.