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）拥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迅速建立。越来越多的证据表明，共生微生物群在胃肠道上皮屏障和宿主免疫功能的发展中起着重要作用。然而，对奶牛GIT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尚未得到很好的研究。新生小牛从母亲和周围环境中获得胃肠道中的微生物。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先天免疫基因表达的显著差异。这些群落不仅仅反映了与食糜相关的群落，这表明宿主在建立这些群落中起着重要的作用。对人类和老鼠的研究表明，一旦微生物群落建立起来，这个群落的“足迹”就很难改变，除非是暂时的。反过来，宿主-微生物的相互关系在维持肠道稳态中起着调节作用。粘膜上皮是宿主与肠道环境之间的屏障，它在识别胃肠道微生物组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起着关键作用。我建议使用功能基因组学方法来研究宿主在小牛胃肠道中宿主-微生物相互作用中的作用，该方法基于这样的假设，即宿主对奶牛早期微生物定植和副产物的识别可以调节胃肠道上皮屏障功能的发展。本研究的目的是：(1)确定肠道微生物群、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犊牛肠道微生物群屏障功能的影响。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，并在未来的应用中改善动物肠道健康，以实现加拿大更可持续的动物生产。

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.