Microbial Influence on Mucosal Homeostasis

总结/摘要 胃肠道粘膜作为腔内容物和下层组织之间的界面起作用 因此，它在维持粘膜和全身稳态中至关重要。肠腔容纳了 数量庞大且分类多样的原核微生物群。在健康状态下，粘膜和微生物群茁壮成长， 在一个互利的共生安排。宿主和微生物都进化出了一个复杂的系统， 相互感知、反应和反应。这些事件部分是由肠道的能力介导的， 上皮细胞通过产生活性氧（ROS）对微生物群的特定成员作出反应， 其用于激活参与维持肠道内稳态的多种细胞途径。这项建议 将采用体内系统，包括广泛使用无菌小鼠，或用 已知的ROS诱导细菌。此外，新生小鼠中微生物群的分类学分析将用于 鉴定对肠粘膜有功能影响的其他细菌。该提案将研究微生物对 已知的和新的信号传导途径，并表征对肠道存活，分化和 增殖我们的总体目标是定义参与者、事件和过程， 宿主微生物接触以及这种相互作用如何影响肠道内稳态、发育和 赔偿ROS和氧化还原刺激途径可能代表了一种保守的机制， 与其肠道微生物群相互作用，因此为治疗操作提供了有吸引力的靶标。

SUMMARY/ABSTRACT The gastrointestinal mucosa functions as an interface between the luminal contents and the underlying tissue compartments, and is thus vital in maintaining mucosal and systemic homeostasis. The gut lumen houses a numerically vast and taxonomically diverse prokaryotic microbiota. In health, the mucosa and microbiota thrive in a mutually beneficial symbiotic arrangement. Both host and microbe have evolved a complex system of mutual perception, response and reaction. These events are mediated in part by the ability of the intestinal epithelia to respond to specific members of the microbiota by the production of reactive oxygen species (ROS), that serve to activate multiple cellular pathways involved in the maintenance of gut homeostasis. This proposal will employ in vivo systems including extensive use of germ-free mice, or mice gnotobiotically colonized with known ROS inducing bacteria. Additionally, taxonomic analysis of microbiota in neonatal mice will be used to identify other bacteria with functional effects on the gut mucosa. The proposal will study microbial influences on known and novel signaling pathway, and characterize the regulatory effects on gut survival, differentiation and proliferation. Our overall objectives are to define the participants, events, and processes involved in host microbial contact and how this interaction influences intestinal homeostasis, development and restitution. ROS and redox-stimulated pathways likely represent a conserved mechanism by which the host interacts with its commensal microbiota, and thus presents an attractive target for therapeutic manipulation.