Understanding the impact of the host on microbial ecology and host functions in the gastrointestinal tract of calves using functional genomics

哺乳动物胃肠道(GIT)含有动态和丰富的微生物种群，这些种群在出生期间和出生后立即迅速建立。越来越多的证据表明，共生微生物区系在胃肠道上皮屏障和宿主免疫功能的发展中发挥着重要作用。然而，对奶牛胃肠道中宿主-微生物相互作用的了解有限，其在动物健康中的作用也没有得到很好的研究。新生的小牛从它们的母亲和周围环境中获得了肠道中的微生物。我的实验室最近的研究表明，粘膜相关细菌群落的差异导致天然免疫基因表达的显著差异。这些社区不仅反映了与Digesta有关的社区，还表明在建立这些社区方面发挥着重要的东道主作用。来自人类和老鼠的研究表明，微生物群落一旦建立，除了暂时的变化外，这个群落的“足迹”很难改变。反过来，宿主-微生物之间的相互关系在维持肠道内环境平衡方面起着调节作用。粘膜上皮在宿主和肠道环境之间提供了屏障，在识别GIT微生物群和调节微生物副产物以及微生物细胞，特别是病原体的通过方面发挥了关键作用。我建议使用功能基因组学方法来研究宿主对犊牛胃肠道中宿主-微生物相互作用的作用，该方法基于这样的假设，即宿主对奶牛早期生命中微生物定植和副产物的识别可以调节GIT上皮屏障功能的发育。本研究的目的是1)确定肠道微生物区系、上皮屏障(紧密连接)和粘膜免疫功能之间的相互作用；2)利用功能基因组学分析确定日粮对与微生物区系相关的屏障功能的影响。这将有助于了解反刍动物中宿主-微生物相互作用的基础知识，以及未来在加拿大改善动物肠道健康以实现更可持续的动物生产的应用。

The mammalian gastrointestinal tract (GIT) harbours dynamic and abundant microbial populations and such populations are rapidly established during and immediately after birth. There is increasing evidence that commensal microbiota plays an important role in the development of the GIT epithelial barrier and host immune functions. However, the understanding of host-microbial interactions in the GIT of cows is limited and its role in animal health has not been well studied. Newborn calves acquire microbes in their GIT from both their mother and the surrounding environment. Recent studies from my laboratory have demonstrated that differences in the mucosa-associated bacterial community resulted in significant variation in expression of innate immune genes. These communities did not simply reflect those associated with digesta indicating that there is a significant host role in establishing these communities. Studies from human and mice have shown that once the microbial community is established - the "footprint" of this community is very difficult to change except temporarily. In turn, the host-microbial interrelationship plays a regulatory role in maintaining gut homeostasis. The mucosal epithelium provides a barrier between the host and the gut environment and it plays a key role in recognizing the GIT microbiome and regulating the passage of microbial byproducts as well as microbial cells, especially pathogens. I propose to investigate the role of the host on host-microbial interactions in the GIT of calves using a functional genomics approach based on the hypothesis that the development of epithelial barrier functions of GIT can be regulated by the host recognition of the microbial colonization and byproducts in the early life of cows. The objectives of this study are 1) to identify an interplay among gut microbiota, the epithelial barrier (tight junctions), and the mucosal immune function, and 2) to identify the effect of diet on the barrier functions related to microbiota in dairy calves using functional genomics analysis. This will contribute to the fundamental knowledge on host-microbial interctions in ruminants and future applications to improve animal gut health for more sustainable animal production in Canada.