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

调节肠道微生物组生态的因素及其对结肠免疫的影响

• 批准号: 402641-2012
• 负责人: Gibson, Deanna
• 金额: $ 2.4万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2017
• 资助国家: 加拿大
• 起止时间: 2017-01-01 至 2018-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=630110
• 关键词: Factors; modulate; ecology; intestinal; microbiome

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.

肠道微生物组是一个复杂多样的微生物环境，它为宿主的肠道环境贡献了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相处，在新生儿肠道免疫反应的发展中起着重要作用，并被认为维持成人肠道处于生理炎症的受控状态。考虑到微生物群位于肠道粘膜的间期，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，因为肠道微生物组的组分在局部和全身免疫的早期发展中起着至关重要的作用。事实上，在IBD、肥胖症和糖尿病等各种疾病表型中观察到了生态失调或改变的微生物种群。了解可以影响微生物组生态的因素，如营养，体力活动和衰老过程中肠道微生物组变化的动态，可以深入了解每个细菌种群在肠道稳态中所起的作用。在这种情况下，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。我假设我们目前的饮食模式和体力活动的减少会对肠道微生物组产生不利影响，并改变肠道免疫反应。在肠道炎症的对照和小鼠模型中使用基于饮食和运动的干预措施，以及体外技术，我们将检查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;和iii）比较从新生儿期到老年期的效果，并确定这些生态和免疫学变化是暂时的还是长期的。