Defining How The Intestinal Microbiota Responds to Pathogen-Induced Inflammation

描述（由申请人提供）：驻留在我们胃肠道中的10-100万亿微生物形成了一个复杂的微生物群落，称为微生物群。肠道微生物群主要由互利共生的细菌组成，这些细菌在人类健康中发挥着许多重要作用，包括帮助消化和帮助抵御病原菌引起的感染。然而，对于常驻微生物抵抗病原体入侵或适应与感染（如炎症和腹泻）相关的生理变化所采用的策略知之甚少。该项目的重点是了解我们的居民微生物群成员如何抵抗或适应由肠道病原体沙门氏菌引起的肠道炎症。肠道居民互惠分子的转录谱将用于识别参与炎症反应的重要途径。模型肠道互利主义者多形拟杆菌的遗传操作将与体内方法相结合，该方法利用定殖有定义的简化微生物群落或定殖有完整人类微生物群的gnotobiotic小鼠来定义相关途径和这些途径的功能。这些研究将揭示肠道病原体出现的机制，并确定体内沙门氏菌感染期间微生物群所采用的功能适应。通过了解这一过程，对抗和预防此类感染的新战略将变得显而易见。

DESCRIPTION (provided by applicant): The 10-100 trillion microbes that reside in our gastrointestinal tract form a complex microbial community known as the microbiota. The intestinal microbiota is largely composed of mutualistic bacteria which play many important roles in human health, including aiding in digestion and helping to fend off infection caused by pathogenic bacteria. However, little is known about the strategies employed by resident microbes to resist pathogen invasion or adapt to physiological changes associated with infection such as inflammation and diarrhea. The focus of this project is to understand how members of our resident microbiota resist or adapt to intestinal inflammation caused by the enteric pathogen, Salmonella enterica serovar Typhimurium. Transcriptional profiling of gut-resident mutualists will be used to identify important pathways involved in response to inflammation. Genetic manipulation of the model gut mutualist Bacteroides thetaiotaomicron will be combined with in vivo approaches that utilize gnotobiotic mice colonized with defined simplified microbial communities or colonized with a complete human microbiota to define relevant pathways and the functions of these pathways. These studies will shed light on the mechanisms that underlie the emergence of intestinal pathogens and identify the functional adaptations employed by the microbiota during Salmonella infection in vivo. By understanding this process, new strategies to combat and prevent such infections will become evident.