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多样的微生物环境，其贡献是100倍以上 遗传物质进入宿主的肠道环境，与之密切相互作用。微生物区系通常与肠道和谐相处，在新生儿肠道免疫反应的发展中发挥重要作用，并被认为保持成人肠道处于受控的生理性炎症状态。考虑到微生物区系位于肠道黏膜的间期，微生物区系生态的变化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系统免疫的早期发展中发挥着关键作用。事实上，在IBD、肥胖症和糖尿病等各种疾病表型中都观察到了微生物种群的失调。了解影响微生物群落生态的因素，如营养、体力活动以及肠道微生物群落在衰老过程中的动态变化，可能有助于深入了解每个细菌种群在肠道内稳态中所起的作用。在这种背景下，我的研究目标是了解环境决定因素对肠道微生物群的影响。我假设，我们目前的饮食模式和体力活动的减少对肠道微生物群进行了不利的调节，并改变了肠道免疫反应。使用节食--和 通过采用控制肠道炎症的运动干预措施和小鼠肠道炎症模型，以及体外技术，我们将检查i)饮食和运动等生活方式因素对改变肠道微生物区系生态的影响；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，并确定这些生态和免疫学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 more genetic 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- and exercise-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.