The role of intestinal microbial metabolites in regulation of host physiology

哺乳动物的肠道里生长着大量的微生物。个体之间的微生物群落结构有很大的差异，在过去的十年中，越来越明显的是，这个群体在塑造宿主生理方面起着重要作用，尽管通过很大程度上未表征的机制。当食物被消耗时，微生物会积极代谢食物成分，从而产生各种分子，这些分子有可能影响宿主的生理。我建议研究如何选择微生物群体的成员通过系统地从肠道中清除细菌群体来影响影响宿主的分子的产生。我们将测量微生物种群的变化如何影响信号分子的产生，并随后改变宿主生理。本研究的发现将为我们的微生物共生体的生态学和代谢活性提供新的见解，并发现新的生物活性分子以及参与宿主微生物调控的宿主信号通路。在描述微生物与哺乳动物相互作用的基本原理时，我们将开始了解微生物群的变化如何影响宿主。对微生物促进肠道生理的方式有了更好的了解，将通过提供新的工具和策略来改善人类和动物的肠道健康，并将促进无抗生素动物生产系统，从而使加拿大受益。

An abundant population of microbes colonizes the mammalian gut. There are substantial variations in the structure of the microbial community between individuals, and over the past decade it has become increasingly apparent that this population plays an important role in shaping host physiology, although through largely uncharacterized mechanisms. When food is consumed microbes actively metabolizes dietary constituents resulting in the production of diverse molecules, which have the potential to impact host physiology. I propose to investigate how select members of the microbial population affect the production of molecules that impact the host by systematically removing bacterial populations from from the gut. We will measure how the changes in microbial population affect the production of signaling molecules and subsequently change host physiology. The findings of this research will provide new insights into the ecology and metabolic activity of our microbial symbionts and identify new bioactive molecules as well as host signaling pathways involved in microbial regulation of the host. In characterizing the fundamentals of microbe-mammalian interactions we will begin understand how changes in the microbiota impact the host. Having an improved understanding of the way microbes contribute to intestinal physiology will benefit Canada by providing new tools and strategies to improve intestinal health of both humans and animals and will facilitate antibiotic free animal production systems.