Factors which modulate the ecology of the intestinal microbiome and the effect on colonic immunity

肠道微生物群是一个复杂而多样的微生物环境，它为宿主的肠道环境提供了100倍以上的遗传物质，并与宿主的肠道环境密切相互作用。微生物群通常与肠道和谐共存，在新生儿肠道免疫反应的发展中发挥重要作用，并被认为维持成人肠道处于受控的生理炎症状态。考虑到微生物群位于肠道黏膜的间期，对微生物群生态的改变可能会对宿主的免疫反应产生重大影响，并产生广泛的后果，因为肠道微生物群的组成部分在局部和全身免疫的早期发育中都起着至关重要的作用。事实上，在IBD、肥胖和糖尿病等多种疾病表型中都观察到生态失调或微生物种群的改变。了解影响微生物生态的因素，如营养、身体活动和衰老过程中肠道微生物群变化的动态，可能有助于了解每种细菌在肠道内稳态中所起的作用。在此背景下，我的研究目标是了解环境决定因素对肠道微生物组的影响。我推测，我们目前的饮食模式和体力活动的减少对肠道微生物群产生了不利的调节，并改变了肠道免疫反应。利用饮食和运动干预控制和小鼠肠道炎症模型，以及体外技术，我们将研究i)生活方式因素，如饮食和运动，对改变肠道微生物群生态的影响；Ii)这些生态变化对肠道炎症的影响；iii)比较新生儿和老年期的影响，确定这些生态和免疫变化是短暂的还是长期的。

The intestinal microbiome is a complex and diverse environment of microbes that contributes 100X moregenetic material to the host's intestinal environment with which it intimately interacts. The microbiota normally lives in harmony with the intestine, plays a significant role in the development of intestinal immune responses in neonates, and is thought to maintain the adult intestine in a controlled state of physiological inflammation. Considering the microbiota resides at the interphase of the gut mucosa, alterations made to the microbiota's ecology likely have a significant impact on the host's immune responses with wide-ranging consequences since components of the intestinal microbiome play a crucial role in the early development of both local and systemic immunity. In fact, dysbiosis, or altered microbial populations, has been observed in various disease phenotypes like IBD, obesity and diabetes. Understanding factors that can influence the ecology of the microbiome, such as nutrition, physical activity, and the dynamics of intestinal microbiome changes during the process of aging, may offer insight into the role each population of bacteria plays during intestinal homeostasis. In this context, my research goals are to understand the impact of environmental determinants on the intestinal microbiome. I hypothesize that our current dietary pattern and decline in physical activity adversely modulates the intestinal microbiome and changes intestinal immune responses. Using diet- andexercise-based interventions in control and murine models of intestinal inflammation, and in vitro techniques, we will examine i) the effect of lifestyle factors, such as diet and exercise, on changing the ecology of the intestinal microbiota; ii) the impact of these ecological changes on intestinal inflammation; and iii) compare the effects from neonate to geriatric periods and determine if these ecological and immunological changes are transient or long-term.